With the release of Drupal 6.0, there have been major steps forward in the theme layer. Two of the most important are the standardization of template files and their associated pre-process functions, and the addition of theme.info files which allow the overriding of whole core stylesheets.
This Sunday I gave a 45 minute overview lesson on these topics for The Drupal Dojo. There will be more later, but in brief I think with this core advance, all that remains for Drupal to be a truly designer-friendly platform is better documentation of best practices.
Check out the screencast for details.