Maybe I'm being a bit naive here, but I use Ccleaner once every month or two in the belief that this will keep the whole machine as fast as possible. This of course isn't just about the registry, but deals with quite a bit of other crap.
I know that there are others who advocate saving all docs and reinstalling Windoze and all software every so often. Undoubtedly does the trick, and reminds one of how fast a machine could be, but boring in the extreme, and loses half a day each time.