If you want to heavily customize your themes, you probably want to start with themes such as blank slate or twitter bootstrap. However, for a quick prototype or if your need are relatively simple, you can override wordpress's base themes (2012 and 2011) relatively easily and the nice thing a lot of things are customizable from the admin.
To Create a child theme, simply create an empty directory with your theme's name and put the following in a file called style.css:
Theme Name: Your child theme name
Theme URI: http://www.example.com
Description: This is my child theme
Author: Your name here
Author URI: http://www.yoururlhere.com/