I'd say most of the time cleaning the registry does absolutely nothing speedwise and you can in fact do more harm. Some registry keys they detect may not be in use at the moment, but may be required for a future function. If you do mess with a needed entry, you'll have a nightmare troubleshooting down the line. Computers can access the registry so quickly that removing items or compact it really does nothing you'd notice. It's all placebo. If your computer is working fine, don't touch the registry.
It does have the occasional use however. Some progrmas can leave annoying context menu items, or unwanted behaviour by not uninstalling properly. A registry cleaner can quickly resolve these unwanted entries without having to search manually.
Also, on really old installs (few years old for example), registries can become quite large with deleted entries and unoptimized space. Something like ERUNT might be useful then, to bring it back down to a smaller size, or a registry cleaner, but again if you weren't having any issues I doubt you'll notice a speed difference - perhaps a little less ram being used.
Overall I'd say don't use a cleaner unless your install is really old or has issues connected with the registry. ERUNT and NTREGOPT should be enough in most cases if you want to reduce its size.
