If you don't mind paying for a registry cleaner, Registry Mechanic is the best for it's simplicity, safety and power. You just click scan and it scans without need of user intervention and removal is just as quickly as pressing the fix button. It's got a nice clean interface as well.

The problems I have had with Registry Mechanic is I feel it isn't updated as much as it should be. Certain errors get undetected for long periods of times. It also freezes at times and can be very slow to finish scanning.

This is a product anyone who has time, patience and doesn't mind spending money should have. It will work for anyone regardless their user experience.