RPLUSJ  Twitterrific is an excellent desktop solution for Twitter, especially for users who are looking for a minimalistic user-interface and have no desire to spend hours every day organizing follower groups or engaging in endless back-and-forth conversations.

If your workflow is like mine, you simply want to get your updates quickly and post a Tweet with as little hassle - and in as few key strokes - as possible. Twitterrific does this with a simple keyboard shortcut. It's easy on the eyes, well designed from a UI point of view, and is light on resources.

Sadly, the Mac version is being neglected by the developers and is lacking at least one useful feature for "speed" users, like myself... a retweet shortcut. Search would be a nice addition, too.

If you don't want to pay to register the app, Pwitter is a similar, free program, albeit not quite as pretty.  
(Version 3.2)