I find Uninstaller 2008 a good registry cleaner its not actually a reigisty cleaner, It tracks the uninstallation and removes any traces like registry keys, values, and orphan files after uninstallation. Way better than the normal add & remove that windows has. When this sucker cleans, IT CLEANS!
Just to test it i uninstalled a game through the Add&Remove windows tool then i got uninstaller 2008 to check and it found 48 registry files related to the game and removed them. Add&Remove missed them. Of course if you not going to uninstall anything then this program is probably not needed as much but its the best registry cleaner.
Other than that if my pc starts to slog real bad i use the best cleaner known to man. A reformat. Split your hdd into two move everything you want to keep to the 2nd partition or spare drive if you have one and reformat PC, reinstall windows on the C drive. PC will be like new again.