At $19.99 in the Mac App Store it's not the cheapest Twitter client out there but combined with the iPhone or iPad versions, Tweetbot is the best mobile and desktop Twitter experience with one feature alone, never mind all the other cool stuff:

Magically sync your timeline read location, direct message read status, and mute filters with Tweetbot for iPhone and iPad via iCloud.

I haven't decided if I'm going to pick up a copy yet. I think they're fully justified in charging $19.99 for an awesome looking app that I'd use everyday to access a service that has provided a good portion of my business clients. I just am unsure about where Twitter is headed as a company and if my money would be better spent on the coming launch of Netbot for Mac[1].

Screenshots

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[1]: It's not out yet. But with the success they're having with Tweetbot for Mac, it won't take long.