I can't even think of any tweaks that I had to do on any of my Vista boxes. Aside from personal preference settings, such as enabling/disabling System Restore, there isn't much that needs to be done.
The only tweaking I've done is through TweakVI or XdN Tweaker (both of them fixed small annoyances I had is really all it was). Besides that, I haven't really touched it much. I spose if you really want you could check out BlackViper's site.