DestroyTwitter is a full-featured yet lightweight Adobe AIR twitter app. While many other AIR apps are guilty of being on the pudgy and/or sluggish side, DestroyTwitter is refreshingly responsive. Upon load it starts at about 40MB and after using it for a bit, searching, and loading a couple other columns it only climbed to 61MB. Very good for an AIR app!
Even though the memory footprint is light, it doesn't skimp on features. The app is maintained by Jonnie Hallman, an Experience Designer at Adobe, so that may have something to do with it.
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:
Bitter is a lightweight Twitter client built on .NET, so it's Windows only. From the Bitterware site:
It consumes a low amount of memory, is theme-able, is secure (uses HTTPS for authentication and encrypts authentication details), uses a familiar tabbed-interface and so much more!