If my experience was anything to go by, you would never update Windows. Every serious problem on my PCs have been caused by those. On the other hand I have run registry cleaners for years and still going strong.
There are limited benefits. A lot of what they remove does not matter. The fact that different cleaners take out different entries could be viewed as the authors being over-careful in different ways. CCleaner removes almost nothing but that's fine if they are the most useless (perhaps 1 or 2 on average). Most of the entries my cleaner deletes are empty ones (total deletes, about 300 on average).
I have yet to use a cleaner that does not do a backup of the changes.
The only issue I have had is when I updated my cleaner, it removed some entries that it should not have. I undid the changes and reverted to the earlier version of the software. My experience there is once you have a version that works fine on your PC, stick with it.