For the month or so I used dual displays (Dell 2208WFP and ancient Toshiba 15'' CRT) on my Studio 540, I went with extended desktop in the hopes of having Flight Simulator X span the two displays. Well, thanks to Vista, everybody's favorite OS, the main cockpit was only on the first display, with the second limited to instruments.
I've never done it or seen it done with a Mac, other than mirroring with an iMac and projector at school.
If I had multiple displays, there'd have to be an odd number, with all displays being the same model.