So my players' adventuring group Til She Grows A Beard fought and defeated a god this past weekend. It actually was not the one sided bloodbath that I thought it would be but it took alot of work on my part to keep my precious deity from being absolutely crushed. Here are my tips for Kyuss (and AoW in general) All this is 3.5
1. The Sphere of Annihaltion was not that big of a deal. At first I was worried about this artifact but Kyuss is amply prepared to deal with this. He is capable of casting gate on it which more than likely cancels it. (best result for him would be the planar tear result as he is dimensionally locked ala Manzorian/Tenser) Also he is more than capable of opposing control checks, especially after gating in something that can make opposing disarm checks on a talisman of the sphere wielder (which is usally a wizard with a horrible check). I went with Nightwalkers for this. Nightwalker/Blackguards actually.
2. If you let your players use something other than the PHB, you use it too! This is where most of my work came from. Nearly every encounter that I ran in the whole AP was completely retooled. The AP can not assume that every player has access to any sourcebook, so every encounter would be trounced by splatbook wielders. If you want to be a "pick up and play" DM, be prepared to say no to pretty much anything and everything.
3. At high levels, not everything is explained well. This is kind of Nit-Picky, but its a pretty big nit to me. Miracle allows you to Restore all your fallen allies to life. Oh yeah? all of them? ever? with no level loss? as Raise Dead? as True Resurrection? I dont know. Also, the Bead of Summoning from a Greater Strand of Prayer Beads allows you to summon an extraplanar ally of your diety. Hunh. As Gate? Summon monster? In short, be prepared to come up with answers on the fly. (BTW, I went with as Raise Dead, but massed and without material components, and as Summon Monster 9)
4. Lastly, and especially if you followed #3 above, do not be afraid to go over the top with your encounters. Seriously. Even if you think an encounter can not be defeated, your players will probably find a way. This may not work with every group, but my group was not afraid to run away and come back with a new strategy.