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.