Yesterday, Flickr released a new version of their Flickr Uploadr. Since version 3 the Uploadr has been based on XULRunner, the technology with powers Firefox, Thunderbird, Miro, Songbird and TomTom's GPS desktop software, which means that it's possible to install extensions.
There doesn't appear to be many extensions out there - in fact, the only one I've found is Image Preview. But there must be a whole load of possibilities for extending the Uploadr - geo-tagging, basic photo editing (cropping/resizing), tag suggestion etc. And I'm sure someone will come up with a way of changing the theme.
I use Flickr Uploadr for all my photos and love it. The idea of being able to geo-tag interests me immensely seeing as my camera doesn’t support it.