I differ from other opinions. Certain times left over registry entries, usually the driver references, affect computer speed. While it requires significant experience with manipulating registry organization, registry cleaners can help removing remanants much more easily so that you do not have to manually remove.
I find CCleaner's registry cleaner to be safe with average users. JV16 Powertools and Iolo Registry Mechanic are extreme level of registry cleaner and cause give you more problems if used incorrectly or without deep understanding. Also, not all backup registry will plug-in back smoothly. Hence for non-technical people CCleaner is enough to clean registry. I agree that CCleaner cleaned registries may not improve computer functionality.
I often use RegAlyzer to "hunt" for remnant registries that are not cleaned when a program has been removed from Control Panel / Uninstall.