A very good and safe way to clean one's registry is to use the Registry component of Piriform's CCleaner. Then to defrag the registry I use Macecraft's jv16 Powertools. Defragging the registry can save a few kilobits of data - making the computer seem just a tad bit quicker. Also a system defrag is a good idea too.
NO! Do NOT mess with your registry anything that automatically does ANYTHING to the registry that is not directly from Microsoft I would deem as more a nuisance than an angel. It MAY seem to benefit you first run, but after awhile when your computer is failing to find anything you will have lots of problems upon continual usage of such tools. NEVER run automated Registry defrag/cleaners or anything, especially without the knowledge to WATCH what it is doing.