The main difference in general performance is that with Keyclone the small windows were rendering at that actual size. With ISBoxer, the small windows are rendering at the full size (size of the main window) as long as Swap is enabled in your Window Layout. If you would rather they render at the small size, you can disable Swap, but you're also going to lose mouse broadcasting in this trade-off.

In other words, with Keyclone an example setup on a 1680x1050 monitor might have a 1344x1050 main region with 4 336x262 smaller regions. The smaller regions are actually rendering at 336x262, which uses less GPU time (aka renders faster) than the full 1344x1050. The same layout using ISBoxer and having Swap enabled, all 5 of those regions are rendering at 1344x1050. The time it takes to render all 5 is greater, so your FPS will take a hit. Most people seem to like the instant swapping enough to switch to performance settings instead of looking at shinies when multiboxing

Also, I repeat this ad infinitum as it tends to evade, well, everyone. You will get a great performance increase by aiming the camera on your non-main characters downward, so you have a top-down view. Casting targeted AOEs is also easier this way, since the camera should already be downward on the alts.