I just wanted to throw in my two cents to say I’ve been using CCleaner for years, regularly cleaning everything including my registry, and have never had it cause any issues whatsoever. I understand people’s desire to recommend safe courses of action and modifying your registry is potentially one of the most unsafe things you can do, but I’ve found CCleaner’s registry cleaning to be completely safe, every time.
That said, I have had a driver-cleaner program screw things up for me. At one point I ran one to clean up my ATi drivers after switching to an nVidia card and that turned out to prevent me from installing Service Pack 1 for Windows 7. Turns out that because the ATi drivers that come with Windows are now missing, SP1 fails to install (at the very end of the 20+ minute install process, of course!) and as far as I can tell there’s nothing I can do about it short of reinstalling the OS. Though I tend to blame this failing more on Microsoft for hinging the installation on something as stupid as the presence outdated drivers for a video card I don’t have.
TLDR: driver-cleaners iffy, CCleaner awesome.