If you are starting a new WordPress project in 2012 you should consider building it on top of a starting theme. For some time Boilerplate theme for WordPress is what I’ve been using to reset the browser to sensible defaults and take advantage of best practices that come baked into HTML5 Boilerplate.
I am happy to report there is now a starting theme that is even better, which is called Roots.
Roots wraps HTML5 Boilerplate with Blueprint CSS (or 960.gs) and barebones Starkers theme & comes with handy URL rewriting features. It is probably the most complete package of this kind at the moment.
It has a nice website too:
