A lot of sophisticated twitter clients are written in Adobe AIR. This has the advantage that that client can run on multiple platforms, but also has certain disadvantages like that the UI isn't like a real Mac (or Windows) program, and the behaviour of the application can be different than a native app.
So, after trying Twhirl, TweetDeck I ended up installing and running Nambu, and haven't looked back since.
The new update includes a new UI, which allows for multi-column view. You can add or remove columns at will and you can also re-order them. The UI is nice and clean, and easily readable, in contrast to TweetDeck for instance, which makes my eyes hurt trying to read it.
Another new addition is the use of friend groups. Here you can create groups of twitter friends so you can follow only those specific tweet updates.
The application also has a lot a bugfixes and seems faster too.
However, there are still some things missing, but the developers seem to be keen to listen to people and implement desired (if useful) functionality pretty soon.
Personally I'd like to have a threaded discussion view, or at least a way of going through replies in an organised way.
Also, you cannot put your friend groups in the column view.
What can I say, if you want to use a nice and native Twitter client on OSX, Nambu is a good step in the right direction. It's not fully grown up yet, but it has a lot of potential.