If I have framerate issues, I will look up the game online and find out which settings have the greatest effect on performance or the smallest effect on quality. I find that shadows are often very demanding but setting them to the lowest setting (that isn't "off") doesn't make a huge visible difference. AA is another really demanding one; it has a pretty noticeable visual effect but I'd still rather go without AA than have low FPS. Whereas there are a lot of settings that barely affect performance even if you turn them all the way up. It also depends on your setup; things like the number of decals (e.g. bullet holes) that remain visible are more demanding on your CPU and RAM, whereas other settings tax your video card.
Also, I prefer native resolution + medium settings over lower resolution + high settings. I got Crysis recently and at 1080p, I can run it acceptably well with high settings, and I prefer that over dropping the resolution in order to get decent framerates with ultra settings.
The other thing is for multiplayer games, I'll turn down the graphics a lot more than in single player games. I keep Crysis at higher settings than BFBC2 for this reason.