Of course, the number-one thing you can do is go get the latest video drivers from ATI and NVIDIA. Get those installed before you start.
Now, I"m not sure if this problem is something everyone already knows about or what, but in the middle of tweaking my system for DOOM 3, I did something I hadn"t for quite a while: put an NVIDIA graphics card in it. (Yes, folks, the Radeon 9800 Pro 256MB card in there was running a little slower than I wanted, so I thought I"d go for the latest. I put in GeForce 6800 Ultra OC.) I was shocked to see performance drop massively with the move to the NVIDIA card. The thing would run OK in some places, but in others, it was literally a slideshow and wholly unplayable. After lots of checking settings, updating chipset drivers, and futzing about, I figured out that the problem was this: I have two monitors on my system. Turning off the output for second monitor (by unchecking "Extend my Windows desktop onto this monitor) immediately fixed the problem. Maybe there"s a more elegant fix—I would like to think so—but that worked for me. If you own an NVIDIA card, you may need to try this.