I'm sure most of those who use Apple would say by erasing windows.
However, those of us who still have to use Windows here are a few suggestions:
I used to use a tool called JV16 power tools: http://www.macecraft.com/jv16powertools2009-info/
It's reg cleaner was VERY aggressive, but I did not have any trouble with outdated and useless entries. That was for WinXP.
Currently I am using a suite from a product Vax recommended to me a while back as a disk optimizer. It now has a full featured suite that I like very much. This is Raxco and the new product is PerfectSpeed 2. http://www.perfectdisk.com/
That is a great optimizer, but I find the reg. cleaner to be limited. I've used this on XP, VISTA and Win7 and it works well on all of them. (note to everyone - this is really a great product for defragging)
There are many, many other small and specialized products, both free and for purchase. These are the ones I've used and like. RegAnalyzer was one I used and wasn't impressed with. But other than that, that is my experience with them.