Clean It Time

tuneup utilities.
http://www.tuneup utilities.com
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Yes TuneUp Utilities is one of the best programs but not free.
http://www.tune-up.com/products/tuneup-utilities/highlights/

I have noticied since I started answering questions, that nobody really want to pay for anything. Lots of them want the best in the world as long it is free.

You could install Advanced System Care. It is free and not a bad program al all.
http://www.iobit.com/advancedwindowscareper.html

When you want one of the best registry cleaners, you can download Comodo Registdry Cleaner. It is free, trustworthy and safe to use
http://registry-cleaner.comodo.com/
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You mean for tweaking settings?
I always liked tweakXP

Or you mean like keeping the registry clean of unused keys and folders?
For that, i suggest yourself.
Those programs never seem to work for me, and they delete things i need.
References :
http://www.tweakxp.com/

I don’t know what the best one that you can "buy" is, but if you want to try a free one that works pretty good then check out

http://www.download.com/Glary-Utilities/3000-2094_4-10852138.html

Glary Utilities offers numerous powerful and easy-to-use system tools and utilities to fix, speed up, maintain and protect your PC. It allows you to clean common system junk files, as well as invalid registry entries and Internet traces.

You can manage and delete browser add-ons, analyze disk space usage and find duplicate files. You can also view and manage installed shell extensions, encrypt your files from unauthorized access and use, split large files into smaller manageable files and then rejoin them. Furthermore, Glary Utilities includes the options to optimize memory, find, fix, or remove broken Windows shortcuts, manage the programs that start at Windows startup and uninstall software. Other features include secure file deletion, an Empty Folder finder
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