I'm just wondering if anyone here has any input on how leaving and returning would impact the game.
They left in the brain room (after defeating it) to go back to town and rest, but I don't want the rest of the dungeon to be a cakewalk now. I decided to swap the BBEG for a psionic version to make things a bit more harder and/or interesting, but the only other encounter really left is the Advanced Octopin/Vrock.
So any input on creatively re-populating the first few segments that would make sense at this point?
I don't know how powerful your group is, but believe me, a prepared and ready Zyrxog is really, really dangerous!
My group has insanely high stats (like point buy 53, don't ask) and I have 5 players. They knew what they had to expect (except of course his spells: like empowered lightning bolts) and still they had a very hard time winning. Zyxog additionally is very proud of himself, so I guess he would make his remaining monsters bar up the doors again and wait for the PCs to deal with the problem himself once and for all.
I had him place some nice gifts on the PCs doorsteps however, so they knew that he knew!
In his mind he could still recruit more minions later. If you really like, you could still rule, that Zyrxog has some rogues and street toughs as minions left and maybe one or two drow who were on patrol.
I had him round up an assassination attempt on them that night, while they slept at the Crooked House. From memory, a bunch of Octopins, with at least one high level Drow on a Nightmare. The PC's won after a very tough and interesting fight, but were kicked out of the place for inciting trouble. Made the next day interesting, and as others have said even Zyrzog by himself (I added the advanced Octopin, I think) can be quite tough, depending on PC tactics (my Fighter saved vs mind blast and flew to him, so it wasn't devastating).