Twhirl is my Twitter client of choice. It’s lightweight and it has a respectful feature set. Twhirl runs on Adobe AIR, and therefore will work on Windows and Mac OS X. (Linux too, but if I remember correctly, Adobe AIR is a little buggy on Linux.)
Twhirl notifies you of incoming tweets, marks those you haven’t read yet, and offers Friendfeed support as well as Twitter. It has several URL shortening options built-in, including the very short Is.gd, and TwitPic support exists.
A handy “Retweet” function is included along with the Reply and Direct message buttons.
Nearly any day-to-day Twitter task can be done through Twhirl. It’s a simple and elegant solution for desktop Twitter usage, and one I highly recommend.