Hands down the best performace booster I have found besides just defraging is
RegSeeker. It's a real small registry cleaner. I heard about it a while ago on TechTV and have been using it ever since with no problems. They keep updating it also. It is absolutely wicked.
Run it (it automatically backs up all the changes also), and restart you computer and watch it start in about half the time and run a ton faster.
Basic directions are run the registry clean option, select all that it finds, and delete it. I know it sounds scary but it does back everything up. I've never had any problems with it.
Other stuff I use:
- AV: Norton
- Spyware: Spybot and Ad Aware both
- Firewall: Zone Alarm