Just some thoughts as I am about halfway through running this one...
Due to the sandbox nature of the path, there's no 'rails' guiding the party along from point to point. But it should be possible to get a sense of the probable structure and contingencies, especially if you know your group well enough to anticipate their approach. I wish there had been space for more of an exploration of this within the module, though.
Is it really likely that any group of players is going to sit back and fight off the blooms without trying to do anything to find Nyrissa? The module covers this contingency with its "second round of blooms" idea, but it seems far more likely that they'll make a beeline to Thousandbreaths as soon as possible. (Granted, this makes the encounters there more dangerous.)
As the GM, your control over this part of the plot hinges on how much information you give them. How much does Evindra tell them? How soon can they figure out how to find the gate and use the trophies? My group headed straight for Thousandvoices after the first bloom, but was frustrated by the gate and felt like they were missing something; it's a puzzle that can only be solved by doing nothing other than waiting for the next bloom, and I eventually had to just explain it, which was satisfying for no one.
There's also the consideration that, once they get in, players are likely to keep hammering at Thousandbreaths until everything is dead. At this point, the main factor is stopping to rest vs. having blooms occur, but as published, the blooms are too far apart for a determined group. Even killing one guardian per (15-minute work) day lets them clear things out well before the last half of the month.
Here the GM needs to again decide how much info to give out. Does the party know about uprooting the realm? If not, they'll probably go straight to the House. If so, they will avoid it and systematically eliminate the glade guardians one after the other.
Throughout all of this is the question of how quickly things come back to life in the First World. It would be a huge shock to spend a lot of resources killing Ilthuliak only to come back after resting and have to do it all over again. I wish the module had explained this a bit more than just a mention in the backmatter -- is it even supposed to come into play?
If it does, you have to let the players know how to stop it from happening, and then they will focus exclusively on uprooting the realm. If I were a player and I knew that my impending boss fight with Nyrissa was going to be wasted effort, I'd absolutely put it off until I had uprooted the realm. So this begs the question, won't most groups end up doing that first, and facing a severely depowered Nyrissa? My players are on a course to uproot, and poor confused post-uproot Nyrissa looks like a total anticlimax from here (especially with Briar still in the players' hands).
Well this has been a bit of rambling, so I'll just finish by pointing out a few of the odd little inconsistencies that could confuse players as they figure out how things work. The Horned Hunter not being a bloom ('where's the trophy? we only need one more! why can't we find this one?'). The Shunned Falls not being a glade for uprooting purposes (this one was only an issue for me because I gave the players a special effect as feedback every time they defeated a guardian). And the guardians not necessarily being the glades' primary owners (the smilodons rather than the Misbegotten Troll, the worms instead of the Wriggling Man).
I'm curious to know how other GMs approached these issues, and how things played out. Did any groups simply sit back and wait for all the blooms? Charge in and kill Nyrissa before uprooting?
I'm running this campaign right now as well. My guys are only just now entering the 4th book so I can't say with certainty what they'll do but I will say that I've looked ahead and seen some of the same issues. I will also note that I always heavily customize the game to respond to my players actions (I eliminated Vordakai entirely) and as a result may not have quite the same game as you.
As far as the matter of how much info the players get I plan to make them work for much of it. By default Evindra will tell them about Nyrissa's existence, what Briar is, and where they can enter Thousandbreaths. She won't be able to tell them about the trophies or blooms but is one of several characters who might be able to identify the effects after they occur.
I've given my players access to numerous characters who know more than they do and allowed them to work out who knows what and how to get that info from them. In one case I made the swamp witch a good deal more knowledgeable about some of what is happening but one of my players took a huge disliking to the attitude I gave her and has since cut that source out of the picture as a potential ally.
A more successful case is when I placed a crown of ashes into the treasure of the baobon sith from the keep but then had my players make a knowledge check to recognize that fey, while magically predisposed to respect the wearer, would heavily resent the knowledge that it was in the hands of a mortal. I also made it clear that if the knowledge were leaked that the characters sold the item it would almost certainly damage their relations with any fey allies. So far they have decided to turn the crown over to one of their known allies but haven't actually done so. When they do they'll get a chance to meet a hamadryad which will promise them a boon after receiving the crown as a gift. She may bargain if they force it on her but this will actually reduce the quality of their reward as I intend to keep her in the background should I as DM need a Deus Ex for later. If the players think to ask her about the green hair they have encountered or even the history of the area and fey in it she will become a clear source of knowledge for them to tap later but she won't be able to give out specifics as a result of "fey law" with teasers to indicate that this may change in the nearby future. Unless they mention Nyrissa specifically she won't tell the players anything about her (They have heard the name once due to my modding a few things but shouldn't make this connection).
I also intend to have Irovetti tease them with the fact that he knows more than they do. If they decide to capture, rather than kill him, they will be able to pry the information out. Irovetti will know that the blooms are coming but not how to stop them and of course knows where Briar can be found (though this may require extreme compulsion to get out of him).
These encounters make the knowledge something the players have to seek out but give ready access to the answers once they know the right questions to ask. I feel just giving them all the info they need straight from someone like Evindra is a bit of a letdown. She should give them enough that they answer a few old questions but come up with new ones. Ones that they can get answered if they think a little about where to ask.
As far as the question of timing out the encounters goes I will make sure that my players know that the longer they are gone the greater the chance of a new bloom while they are off trying to take down the big baddie. If I know them there will be a significant debate over whether they risk leaving the kingdom unattended while they look to put a stop to things especially since a simple knowledge check can tell them that time flows erratically in the first world and the perpetual twilight reinforces this. Again the allies they have made, and the villains they will face, can help if the players choose if they actively seek out the necessary info and ask the right questions. The horned hunter will know full well the effects of the blooms, up to and including the trophies, and even the troll and giants can give indicators about the what Nyrissa intends to do with the blooms. If there any left at the end of the fight with the troll his caged pixies can and will give specific info and can even indicate the effects of defeating glade guardians in Thousandbreaths. Several NPCs and even a decent knowledge check can indicate that the Jaberwock is her biggest punch and not likely to be followed if they reach that point.
I don’t see the creatures from the glades coming back since defeating them is supposed to tear the glade from the realm. I would even consider making the glades themselves disappear after the player’s leave them, so that if they try to return with the same path it takes them to a simple crossroads. No need to tell them that with enough defeated the whole realm uproots. Of course if they have learned it on their own they are welcome to focus their efforts as a reward for having earned that knowledge.
The issue of the glades not being held by the primary focus of their anchor is solvable by having these characters regenerating visibly within the glade. The leftovers become obvious guardians and with them gone the players can strike down the regenerating form by bringing it into contact with the appropriate token(again knowledge that anyone who knows about the bloom effects can share) or even destroyed through mundane means since they are now home(potentially giving them reason to worry about retreating and returning since they may have no way to guess how long such regeneration will take).
Nyrissa, as written, may or may not make a challenge for your party depending on a lot of factors. If you’re worried about her being too easy she is not hard to upgrade since she is far from an optimized build. I know that my players tend to have very effective builds and so I often re-build major villains before they face off. Nyrissa for example can change a fight fairly effectively just by adding pilfering hand to her spell list (BTW she doesn’t have the 10th level ability of mystic theurge listed anywhere and an opening shot of Prismatic Spray & Firestorm at -2 save penalty, followed by a quickened Obsidian Flow can make a great show of power for a climactic battle).
Of course the plot in an adventure for 15th level character does not and cannot work out of the box, if only because parties can be worlds apart in terms of their capabilities, depending both on builds and players' tactical acumen. Some adaptation is mandatory.
In terms of going straight for Thousandbreaths, yeah, considering that Kingmaker demands a fair bit of initiative on PCs' part, this should be expected. You think that PCs might be a bit unprepared for Thousandbreaths without first beating on all the free XP pinatas that compose the blooms, but honestly Thousandbreaths encounters save Ithuliak aren't that diffucult even without defeating the blooms first. If they prove difficult just ignore the "undefeated bloom" bonuses.
As about things coming back to life in the First World, I don't think it is supposed to matter outside of Nyrissa's house, where everyone gets back to life every 24 hours unless you've uprooted the realm.
By the way, I'm not a fan of uprooting. It is too easy to achieve, unless several of Nyrissa's major minions move out of the house to ambush you on one of the glades (and why shouldn't they, considering that uprooting will leave them very vulnerable?) and if achieved it turns the final part of the adventure into cakewalk. With no uprooting on table you have at least some rationale why denizens of the House at the Edge of Time do not actively seek and destroy PCs.