The worst is when it isn't the CPU, but something I/O related like some process reading/writing on the hard disk. This will slow everything down.
Usually the big culprits:
1: The Window search/index service. On Vista, I disable it. Same with XP. Windows 7 and newer, it seems to be better behaved.
2: An AV utility. Since virtually all of them are junk, I just use MSE and Malwarebytes (Malwarebytes can block by IP address, so even 0-days are locked out.) MSE is lightweight. Other brands, can chew CPU and disk, paralyzing even a high end system.
3: AMD/ATI's desktop utility. For some reason, these can memory leak into the gigabyte range (which pushes out all your other programs, forcing your machine to swap.)
4: A backup utility like Mozy, Acronis, or the like.