I would strongly recommend a look at the CSS work done for version 2 of the Plone CMS which you can see in action at http://plone.org/ (Note the clickable letter A's in the top-right corner that alter text size, one of many nice touches achieved with CSS).
They have not only created a default look that I find visually pleasing they have used valid and semantically correct XHTML and CSS ( this short article partly explains the difference ). This forward planning approach allowed them to achieve great accessablity in combination with very flexible skinning through only CSS changes.
You can see a Plone 2.0 site altered purely through CSS here: http://www.tyrell.com/
The main CSS guy from Plone lays out his approach in a talk which you can read the slides of here: http://plone.org/events/conferences/1/archive/customizingplone
Accessability has been a focus for Plone, at a recent conference in Europe they had a demo of a blind Austrian grandmother entering content into Plone through a braille interface after only a brief introduction to the system ( see photos here )