X-Setup Pro

I've used a variety of different tweaking tools over the years, and X-Setup Pro easily ranks in my top 10. Basically it makes a number of different tweaks available in a convenient interface. This program eliminates the need to manually edit your registry and other similar risky modifications. The only downsides to the program is that it isn't actively developed, it costs, and it can be tedious and a bit overwhelming to go through all of the tweaks listed. If you demand total control over your system though, this program is a must. If you are looking for a freeware alternative then I would suggest checking out TweakUI, although it doesn't match up with X-Setup in terms of the sheer number of tweaks available.

As far as features go, this is one of the best tweaking tools. But there is no active development and the price is too steep. I install this on every newly installed system, but there are worthy contenders out there like freshui and tweakui.

Stopped two years ago with the upgrades. Other tweak programs are coming online and would be better to use them instead.

This was once the most complete collection of system tweaks. Sadly it´s lost some of it´s touch with going commercial. It does have the edge of being plugin-based, where the plugins are simple XML files, ie can be written/modified by users.
Containing by now a huge amount of tweaking functions for every halfway decent version of Windows it is still useful.'
I´ve personally developed a habit of spending a couple of hours every time I re-install Windows to walk through the plugins and optimizing my system the way I like it.