I'm already familiar with the PowerToy tool called TweakUI, and also very satisfied with it.
I'm looking for more complete softwares to have even more power over hidden registry settings.
My initial answer was:
After thinking about this further I realize that while that is true that google and regedit gives me tons of power, it isn't the only think I have ever needed.
I believe it is important to go beyond having to use a tool like TweakUI, and instead learn how to work with the registry directly. To accomplish that I think you need to do the following.
Learn to make backups regularly, both of the full registry and the bits you change.
Experiment with changing things within an application, and use your registry backups combined with a diff tool to learn where that application stores its settings. I.E. take a backup, make a few changes in an application, take an new backup, and compare the two backups.
Read, or at least browse through a registry references, or guides to registry hacking.
Once you have a good idea of how most things work you can make educated guesses about how other things work.
You might want to try this question for a list of registry edits without tools.