IMO, many of these things cause more trouble than they're worth. They either don't do the job properly (or effectively, or at all!!), or they aren't used properly by the user, and cause much grief and re-installs.
Cleaning out the junk on your drives, defragging often, turning off Windows functions that you don't need, and minimizing the stuff in the system tray are very good ways to keep your PC in good shape. In the end, though, the best way to get a performance boost out of your PC is to add more RAM, or an SSD, and make sure that your drivers are all up to date.
If you still want to go tweaking and tuning, please make sure to do a full backup first. And most importantly, that includes backing up the registry.
That's my $.02