In 2 years of using Twitter, I have signed up for exactly two third party services: TwitDiff and MrTweet. Both have more or less gone the way of the dinosaur. Conclusion: 3rd party = unreliable.
The web interface started getting progressively worse when they introduced the Ajax interface. Adding gimmicks only serves to add more clutter (I absolutely despise the popup that displays when you hover over someone's tag).
Not sure why I'd even bother, but I might give Hootsuite a whirl soon.
Maybe someone who cares can give a run down of what's out there? What's your killer app Byron, and why?