I don't know how well this works outside of World of Warcraft since I haven't tested it on any other game. If you set your window layout so that there is no cross monitor swapping (in the sense that the clients that are attached to a certain monitor/video card don't swap onto another monitor that is attached to a different video card), then Inner Space is supposed to handle splitting the load between the GPUs. The only way to see if this is working is by using some sort of GPU monitoring tool so you can see if your other video cards are actually doing something besides sitting idle.

As for getting a performance gain out of it, that is dependent on whether the rest of your system, as a whole, can handle more load.