jv16 PowerTools. Actually, I probably should have voted for "more than 1" since I use CCleaner occasionally.
Tweak Now registry cleaner, never had a problem with it, Ccleaner, also very good, only an occasional problem.
On two machines I use a combo of three reg cleaners... jv16 PowerTools 1.3 RegCleaner 4.3 (also by Jouni Vuorio) CCleaner I back up and optimize the registry with ERUNT and NTREGOPT. I find this combination of tools to be very effective and efficient.
I use CCleaner and AusLogics Registry Defrag. I tried many reg cleaners and I have found out, that all good and agresive cause problems and since 1-5% speed improvement is not worth problems, which can result in a few weeks, like BSOD, damaged or slowed Windows or software, I prefer only weak, but safe CCleaner.
CCleaners built in one...use it on messed up systems we're working on. Generally not something I run on a healthy running PCs.
Haven't' used one on a two year old XPx64 installation, face no issues or slowdowns. I don't do much installs and unistalls, only upgrades of programs installed so probably in my case, its not requisite to use a registry cleaner.
I have used RegSupreme Pro for years. I have recently upgraded to jv16 Power Tools 2009, as it was offered free by Macecraft software. With Vista, cleaning old registry entries doesn't seem to have any significant impact in terms of performance as with XP. On the other hand jv16 Power Tools has some tweaks, easily reversible, that can indeed speed up Vista, particularly in shut down time.
CCleaner. I like its passive nature and registry item removal backup, should something go wrong, which never has.
Used to use Eusing, but finally decided to heed most people's warnings. Now it's the less aggressive CCleaner.
FYI - I checked my Regsupreme Pro for updates yesterday, and it said they are discontinuing it, and they will give you a free copy of Jv16 Powertools2009 in a download if you want it.
That's a good deal. Took advantage of it a couple weeks back. Besides it, I also use Hoverdesk's RegSeeker. (I find it curious each program finds different useless registry entries.)