Yeah I know what you mean about registry cleaners. I actually doubt if they really do much though. I have good luck with Tuneup utilities 2008 not screwing things up although the 2006 edition was more problematic and did cause the computer not to boot.
We know one down side of windows is the tendency for it to become slow over a period of time. A big part of that is the registry if you are installing and uninstalling lots of programs. Most power users reinstall windows every 12 months in order to keep that fresh snappy feel. Gamers are very particular about speed and lag and some are really fanatics about reinstall windows every 6 months!!!!!
I really cant prove this, but my "feeling" is utilities like Tuneup will keep your install fast and snappy for a longer period of time before a reinstall is necessary. Maybe doubling the amount of time and of course this really depends on use. But it doesn't make your initial install any better or faster. You can try Tuneup for free for 30 days and see if it works for you. Clean the registry and then run the registry defrag. If you have been running your install for several years and have been installing and deleting lots of programs in that time, you will probably sense a little more "pop" in your OS.
http://www.tune-up.com/products/tuneup-utilities/