Defrag MONTHLY (at least!), or wekly (beter) unless it's a solid state drive that should NOT be defragmented at all.
Use CCleaner periodicaly (monthly is OK).
Run Spybot regularly, but don't forget the virus scan. AVG free is prety good, and FREE!
free.avg.com
Use msconfig to disable unneeded applications and services.
Uninstall old and unneeded programms.
If you have more than 1 drive, move the page file to the second drive, and set it's minimum size to about 1.5x to 2x your amount of RAM.
If you have 3 or more drives, split it across the drives.
Be sure that this drive(s) is thouroughly defragmented before you proceede.
If you don't use hybernate, disable it. It will liberate some place on your drive.
Electro, April 2011