From my experience running 4 monitors on a system with 2 cards (a Radeon 9800 AIW) and another Matrox dual head (64mb, just for video and text) card, there usually are no problems.
The point being here is that you drive a given display with a given card, and if you have games on that particular display, you'd better have the powerful card driving that particular display. Make sense?
E.G. if you want two 22" monitors, are you going to game in both screens at the same time? I don't know of any game that supports that outside of some flight sims, which aren't the most taxing on DX9-type rendering requirements, so I think the answer is: probably not.
Thus, your likely scenario will be that the primary display (the first monitor) will power the games and the gaming output. The secondary display will power the other 'stuff' (documents, etc). However, when I usually started gaming, the other two screens blank out during gameplay.
I hope I'm helping here explaining the issues. Final answer: I don't think you're going to need two cards, no.