Yes, there is no perfect setting for all systems, it varies depending on the Windows OS, applications installed, and more. That is why REG repair sets should always be categorized and sub-categorized. That said, there are more similarities than you might imagine - at least ever since Win9x died, leaving only the NT kernel.
Yes, it is a TERRIBLE idea to just load random REG files from other systems ... which is what people have been BLINDLY doing to try to repair damage for some time. Now they can see what is changing, if anything! So, this is an improvement, SAFER - NOT LESS SAFE. Also, for every 'apply' done there is an undo .REG file created. This will allow changes to be reverted reliably if any problems arise. Not to mention that the user can do their own backup/restore of their hive(s) or select keys.
Anyway, this is no magic bullet to fix all registry problems the world ever had. It is, however, a lot safer than people downloading random REG files on the net and blindly importing them.
Some areas are more OS and environment specific than others. HKCR and shell file association repair, or restore to defaults, is particularly easy and one of the primary targets of the intended REG repair sets I hope the community eventually contributes.
As for HKEY_USERS, no data needs cloned ... That is the base storage for the abstraction of HKEY_CURRENT_USER. Changes to HKEY_CURRENT_USER are automatically propagated into the appropriate location within HKEY_USERS because that is where the actual storage *is*. They can not get 'out of sync'. It is like a symbolic link on a filesystem, if you want to think of it that way. As for propagating user-specific changes to all *other users* on the system, that's beyond the scope and not desired.
It is not as extensive as WinMerge would be, but the concept is similar to any other Diff/Merge type utility.
It is mostly for PC technicians and advanced users. However, if the community puts some effort forth, then REG repair sets can also be useful for end users with no other knowledge. In these cases the trick is categorization to make sure that the REG repair set applies to their system (e.g. it comes from a similar configuration). In that case, that is all they need to know. I had planned to strictly enforce this sort of categorization in some cases, to prevent incidental damage. For instance, using a filename template, do not let users of XP import REG files from Vista -- unless those changes are known to be safe.
Another use is to do a basic 'diff' after running a Registy Cleaner or application install/uninstall -- see what changed, and the cause of possible problems might have erupted. Comparisons like this on the same PC are going to be a big use I believe.