Unless you're having a problem that's the result of an artifact left in the registry (which isn't really that common) there's very little benefit to cleaning the registry up. Most of what's in there is required and typically what gets left behind are keys/values for applications that you may have removed. For the most part programs are accessing hard coded locations in the registry so there's no performance benefit to cleaning the registry. As far as space savings you may reclaim a few MB doing a cleanup which again is trivial.