I might have better ideas if I saw your ISBoxer config For example if you have the background FPS setting set to 60, drop it to 20-30 because there's no sense in trying to get 60 on 5 windows. Also I have no idea what your CPU Strategy selection was, but it's entirely possible that running the CPU Strategy Wizard a couple times and trying different settings will help.

Here's one that's probably not in your config though: do you have the game in Direct3D9, or Direct3D11 mode when you launch through ISBoxer? You have a Direct3D11 card now, so if possible I would be on d3d11 and expect better performance than d3d9. However, either way you can try the opposite to see if it helps any. This old post on isboxer.com has details on switching the game between d3d9 and d3d11: http://isboxer.com/forum/viewtopic.php?f=22&t=774