I've been tossing around a similar idea. I'm considering RPing some sort of civil war within the Seleukid state. The idea here is that you will play as the 'loyalists' who are reduced to a handful of provinces. I plan on giving most of the AS territories to Baktria through FD (and renaming them something appropriate). I might even use cheats to put in appropriate factional MICs before I do it so they can start building armies right away, but that would be a bit more work. The main question is where to place the AS loyalists. Anatolia might be best, but Mesopotamia would also work. If I went with Mesopotamia, I might also give Pontos some of the AS cities in Anatolia and rename them as Pergamon or something (I've already changed them to an East Greek culture). I'd probably leave a few eleutheroi buffers, but I suspect this set up would still get pretty brutal, fairly quickly.

My worst fear about this plan is that it will just result in an uber-Egypt. On the other hand, if you guys have seen them go passive without the Seleukid threat, it might just work.