Short answer: Rarely.
Longer answer: Most of them are not. WindowsSecrets puts out a weekly newsletter that I wouldn't dissuade anyone from subscribing. It's written for users like yourself but I get the occasional tidbit from it as well.
In their latest, they ran a simple comparison of a few well-known system cleaners and, not a big surprise, most made things even worse than before. The only one that didn't was CCleaner from Piriform.com but, for the record, if you try it, do so at your own discretion. There is always the possibility that a registry cleaner will mistake something important as junk.
Full article here at WindowsSecrets.com