I am a part time computer tech and have run CCleaner (with the default settings) on about 500 computers or so if I had to guess in the past year on both XP and Vista and haven't had one single problem as a result. I also pair it up with Registry Mechanic (which is a more thorough cleaner but not free).
Obviously, I can't say that there is a 100% chance that CCleaner can do no harm, but I have never once seen it create any problems...ever.
It does give you the option to back up your registry as well.
