Defrag the drive, disable any unnecessary startup items via "msconfig"
Also check out your temp folders in windows and clear out as much as you can in those..... usually most spyware can be found in those folders.
For XP, there is one in
C:\Windows\Temp and another in your
C:\Documents and Settings\Username\Local Settings\Temp.
If it won't allow you to delete some files, they are currently being used, so restart and hit F8 before the XP splash and go into Safe Mode and delete them from there.
(There is nothing important for OS stability within any of those folders, so don't worry about killing your system if you start deleting things in these folders)
Besides that, running Ad-Aware usually got rid of the rest of the junk.
After that, I'll run the anti-virus, then defrag, restart and my system is usually cleared up pretty good.
Sometimes when you install some programs, they'll also add extra crap on your system too, such as tool bars and search bars..... check out your Control Panel for obvious programs you don't want on your computer and remove them that way.
Other then that, the only other thing I could suggest is get Registry Mechanic to fix up the Registry from time to time.... that too can help speed things up.