I am currently running two 21.5" screens at home. The one screen is a Packard Bell and the other LG, the one screen has a cold look and the other warm. I run both off of one screen, one uses DVI and the other HDMI. You can mix the adapters you use, it will be fine.
When it comes to buying two of the same screens, that is a must, I have been living with these two different screens for a while and the slight height difference, bezel difference, the panel itself being different, all irritate me from time to time.
As far as I know, the new nVidia graphics cards support more than two screens on one GPU now. AMD has been like this for a while now though.
So unless you have a problem with adapters on the back of your GPU/screens not matching up, I'd say mix and match adapters.
With 2 screens, games only use one screen, usually the first screen(most left), the second is unused, so you can throw some widgets showing cpu/gpu usage, or your music player, or watch a show/movie while you game
When it comes to gaming, most games lock the cursor inside the first screen(Some games you can choose which screen to play on, others like AoE II can span both screens, this is very rare though). Some games have the problem where if you move your cursor outside the game's boundaries and click, it will basically minimize as you clicked on the desktop(rare as well, but it happens). When this happens I a program (I think it is called lock cursor, it locks your cursor on a screen while a certain .exe is active).