First thing, turn off Ambient Occlusion if it is on, and then turn your General Draw Quality to 8 (if it is above 8). Those two settings cause 90% of the FPS issues in high-end systems.
With AO off, and draw quality at 8, I was able to max out -every- other setting with NO problems on a i5 quad/GTX460. There is no significant difference between General Draw Quality 8 and 10, and even less difference with 16x AA