Always scan for potential malware, its the cause of many many slow PCs ^^
Another thing, if you have, for example, 1 gig left of space on you 500 GB HDD it WILL be slow, it wont have anything to work with.
Also make sure your processor isnt too hot, it will slow down if it is and eventually break.
Theres A LOT of things that can slow down your PC, my first check is usually scanning my computer, cleaning my PC from all the "residual" files, etc..
Defragmenting should be done at least monthly, and scanning should be done at least once a week.
Using disk cleanup often is also good, it will get rid of most of your unecessary files, not all but most of it.
I would also recommend using ad-aware to scan your PC for malware, i do hope you have an anti virus and a firewall allready installed.
(I know spartan mentioned the virus thing, but i didnt see until i was about to post it ^^)