I think you can with Bioshock over 3 monitors. Microsoft Flight sim can span multiple monitors also, which honestly would enhance the experience.
I have a few monitors and in my experience, PC gaming is best with just 1 nice monitor attached to the computer, unless you are doing the above mentioned. Even having 2 monitors was a problem when playing FPS's just on 1 screen. I know there is software, workarounds, etc, but it just isnt worth it. Also, I've heard it makes some people motion sick.
I like it for WoW though, because I could be grinding and watching a movie/browsing the web at the same time.