The best way to do it is to do it. :) What are you looking to try and do? There are some really good resources to work with the WordPress CSS file (wp-default.css) available:
I think that first link is excellent start in understanding the current WP structure. I'm not a CSS guru and I'm learning it myself (fighting with my footer right now :P); I found by almost erasing the entire CSS file and starting from scratch to be a good "test". Then start dropping in CSS elements (concentrating on one aspect of the design at a time) to get what you want to achieve. If you are stuck on an element, google it. So, if you are having problems with unordered lists, search:
ul (what you want to do) ie
ul align right
PHP is a little more tricky, and it would take more time to understand since it's a programming language. The WP forums are a good resource for a specific issue with PHP that releates to the core script.
So, where to start? What do you want to do first? Create a new design? Create a mockup in an app like Photoshop or even sketch it on paper as far as how you want the elements of the page to look. A lot of times you can find a starting point from an already made template for use/modification:
Current available default templates
Then drop in your design elements and tweak from there. If you get stuck, google it, or ask here. I usually try and answer this type of stuff because it helps myself to learn it a little better. HTH