I'm a rather enthusiastic Remember The Milk user. But even then it's hard to argue that RTM's webapp interface can be a bit cluttered at times. Sadly, using the mobile versions on the desktop proved to be significantly geared towards a touch-interface leaving a bad aftertaste. Besides, they require a RTM Pro account (which I have, but that's beside the point).
Now there was this one horrid Adobe Air app for RTM that shall not be mentioned, but it seems there's a proper one as well: App for the milk. A clean interface, sensible options and just the kind of to-do app to clutter your desktop with. Awesome.