Does not really matter where you start, likely you would create your own CSS shells for the HTML design. These shells can be quickly reworked to be custom. Many of my styles are layered using relative and absolute positions so they can be animated such as http://sdfreelance.vistapanel.net/
If you need to quick start or learn how themes work there are a number of themes which are on the drupal site. A 960 grid html5 theme which is minimal would be sky. http://drupal.org/project/sky Change the “name=” in the info file to remove the name conflict.
Then start designing in PHP language.