On his blog Brandon Beasley has a new tutorial for CodeIgniter users out there on how to create "vanity URLs" that are correctly handled by the framework's routing system.
Recently I worked on a CodeIgniter project that needed the ability to use vanity URLs and display stats about the user represented by the URL. For instance, suppose you want to pull all public data on a user from Twitter and display it within your web application on a customized URL such as http://mytwitterapp.com/brandonbeasley . The difficulty arose when the AUTO setting for URI protocols seemingly failed to handle the PATH_INFO protocol needed for Twitter callbacks and the REQUEST_URI protocol needed for vanity URLs.
His solution combines custom routing on the framework side and a bit of a change to the .htaccess to make the APP_PATH functionality work correctly. Then a simple controller can be created (in his case "User") and the username can be pulled in via the URI helper's segment() function. There's other ways to make this happen with the custom routing CodeIgniter offers, but this method allows for a more fine-grained approach.