I just tested Deskspace on a worst case scenario (Vista 64 bit, Quad Core CPU w/8 gb ram, 2 display adapters, three monitors, every custom tweak imaginable from Fences to Windowblinds) and despite some iteresting behavoirs, it does appear to work without any noticeable slowdowns relating to my Wraith-skinned windows. I can drag them to the screen edges and watch the desktops roll around as expected. Quite a trip on this setup, I must say, but no slowdown seen here.
My setup is similar to yours in many ways, btw.