The safest and one of the best is still the free one.
Regcleaner 4.3.0.780 is still free here:
ftp://ftp.wifak.uni-wuerzburg.de/sy.../RegCleaner.exe
For registry "compaction" and "defragging", use the free NTregopt and ERUNT to make a backup of the registry. Both in this package:
http://home.t-online.de/home/lars.hederer/erunt/erunt.zip
The registry is rarely the cause of the gradual slowdown that computers seem to suffer from. You should scan for ad- and spy-ware and check your Task Manager to see what processes use the most CPU. Do they need to be running (programs---XP services use no CPU unless performing a task)?
And a good chkdsk for disk errors and a complete defrag of the drive, registry, and pagefile will help.
Pagedefrag will defragment the registry hives and pagefile on boot:
http://www.sysinternals.com/files/pagedfrg.zip