Nambu is a feature-rich Twitter app for Mac OS X that supports many social networks. It offers plenty of configuration options but has simple defaults for beginners. It also has excellent integration with its sister services, tr.im and pic.im
Tweetie is a gorgeous, full-featured desktop Twitter client for Macintosh. atebits is the company behind Tweetie, already known for the fantastic iPhone version of Tweetie. Notable features include:
Syrinx is a free, customizable twitter app for the Mac. It's interface is simple yet configurable. You can view a column at a time, either your friends, your @ mentions, or your DMs. Some key features: