Using InnerSpace I can make separate game profiles to have the game instances know which video card to use. There is still a performance hit though. I like a nice crisp 60 FPS so I stick with just the 2 monitors which are hooked up to my primary display adapter. The other two screens are just used for IRC and any other miscellaneous tasks.
One thing I should throw out there though is I am currently using a shitty motherboard that isn't even capable of SLI. So my second PCIe slot is only x4. I haven't gotten a chance to fully test IS's capability with two cards running on x16 slots.
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