Jv16 Powertools has the reputation of being the premier registry cleaning tool among technical types. It was formerly known as RegCleaner
and was free up until about 3 or 4 years ago. If I remember correctly, the developer worked at Microsoft and this utility was even mentioned on some of their website. So technicians who have used this tool for years will still recommend an older version that is still free.
At the time of the conversion I was completely green at using a computer and like many newbies was convinced that there was something wrong with my registry. At a forum that no longer exists now, there was a discussion about how great Jv16 Powertools was and gave links to what was thought to be the last free version, so I gave it a try. I'm not going to relate a horror story here because despite my curiosity I didn't let it overcome my more innate sense of caution.
It is a great tool for someone who knows what they are doing with it. Parts of it can be used safely by your typical end user. But one thing I found out is that the developer must have anticipated that it would go commercial and the versions (yes, more than one) I tried turned out to be time limited. Thus any other version I tried wouldn't work after the initial trial expired.
I was too cautious to ever use the general cleaner. I scanned and looked at the entries that were tagged to be removed--very educational, but time consuming and a lot of it there is not much information on. Still I recommend that the typical average end user avoid using a general registry cleaner--no matter how good they are, they still make educated guesses and when they guess wrong so that you can't boot into Windows then the backups they make will be extremely difficult to get to.
What I found useful about the program is the part that will list software. It dosn't take much skill to know what is no longer installed on a system and using this function is generally safe. Still their are often some programs that are legit that you don't really know about, so caution should still be used here IMO.
You know I have mixed feelings about using a general reg cleaner. On the one hand, they are probably safe to use in most cases. Jv16 Powertools has been in development long enough that it should know what is safe to fix. From what I've read on the net, there is one area, I believe it is 0 byte files that are there by Windows for a reason that will show with a deep scan, that if allowed to be fixed will bork a system. But the "normal" scan should be safe in most cases and there is a little hysteria out there about modifying the registry in any way. That's a normal consequence of the relation of horror stories, but with some education (knowledge is power) so that one is not afraid
of the registry, then it can be dealt with safely. One way to get started on that education is to read BC's tutorial Demystifying the Windows Registry
On the other hand there are some who are looking for a magic bullet and/or are wannabe geeks that don't know when to use the maxim, "If it ain't broke, don't fix it." Commercial reg cleaners will naturally tout cleaning up the registry in order to get one to try and buy their product, but in many cases a reg cleaning is simply not necessary and will improve performance very little if at all.
There are some other misunderstandings--some people seem to think a reg cleaner will remove a malware infection. But cleaners are generally looking for orphans and entires that aren't being used--if an infection is active, then the reg entries are being used and won't show up in a reg cleaner.
Just some of my thoughts, I'm sure there are other opinions.