You CAN run multiple cards independently; however, regardless of whether they are the same model or not, you should NOT use SLI or Crossfire for multiboxing. SLI and Crossfire are designed for running one game in Full Screen mode and may not do anything at all in Windowed Mode. (though I think one of them recently had a driver update to add windowed mode support?)

I've updated ISBoxer.com's multiple video card guide with new info for ISBoxer 38:
http://isboxer.com/index.php/compone...le-video-cards

The new Quick Facts section at the top is relevant whether you're using ISBoxer or not, and pretty much covers all the multi-GPU bases. This stuff hasn't really changed since SLI came out, except for the change in Windows Vista/7