the main reason I use a reg cleaner is to clear out settings keys etc after a program uninstall. Some uninstalls leave these keys behind which means the next time you install the program those settings are used, often I don't want this especially if that program was causing problems or had been munched by a virus.
I've never had JVs regcleaner (or jv16) cause me any problems but I use it fairly confidently because it makes backups of cleaned keys. Its also usefull for manual uninstalls and eliminating startup keys in the case of virus/malware infestation.
Intel core I7 920
6GB OCZ platinum 1600
Samsung 1TB F1 Spinpoint
Samsung SM2443BW 24"