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I have a Mac Pro 2,1 with a modded 5870. I think I may go ahead and upgrade to 10.6.6 to get access to the App Store.

I got the impression that as long as you have a standard card you're okay (i.e. if you have a card Apple doesn't sell then you'd have complications due to identification strings).
 
I have a macpro 3.1 with a ATI 5770 from Apple and no issues after the update. The notes for the update does mention a ATI fix for erratic mouse movements. I guess to be safe back up and try.
 
10.6.6 has a very small, but notable, performance increase. At least on the ATI side. So the GPU drivers are newer.
 
I have a flashed 4890. I updated to 10.6.6 and then installed Netkas QE_CI patch that was released today. It does not fix QE. Things like Preview do not work, the dock animations are choppy, etc. So I would hold off until hopefully Netkas releases an update to today's QE_CI.
 
10.6.6 has a very small, but notable, performance increase. At least on the ATI side. So the GPU drivers are newer.
I did benchtests with XBench and CineBench and 10.6.6 is slightly slower.
MacPro 4,1 with ATI 5870
Open GL Test xB 277 > 247
Open GL Rest cB 28.9 fps > 28.4 fps
 
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HIS 4870 1GB, Wekiva board (reference), custom ROM - works fine under 10.6.6. All cards on the same PCB should work without issues.
 
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