There is no legitimate reason to use any registry cleaner. Some people do it just so they can say that they did, but it has absolutely no effect on Windows performance or functionality. There is, however, a risk that the cleaner will remove entries that are needed, which could cause an application - or Windows itself - to stop working properly.
Having said that, it seems like CCleaner is one of the best at only removing entries that are no longer used. I wouldn't say that it is "safe" since there is always a risk that it will remove something that you need, but maybe just "less risky" than some of the other options.