All icons should be changed with more polished ones, not only toolbar icons. Sometimes they remind me Windows 98. Tango icons are great.
For usability, the real problem is that it has to look good on every platform but that's impossible! Windows, MacOS X, Gnome, KDE, etc… they all have different UI guidelines. Now it's good only on Linux and maybe on Windows: on MacOS X it looks like a mess.
But…
1) I'm not a developer but is it really so difficult to set different actions for the close button on different OS? On MacOS the close button quit the application ONLY when it makes no sense to have the application opened but no window (iLife suite, for example), but when you have an application that you need to use often (like Safari or iWork suite) or that you need to leave open while you are doing other things (like all the other P2P apps) the close button should only close the window, not the application.
2) As said by natsirt, different icon for different files. At least for the most common shared files (movies, archives, etc…).
3) Toolbar customization: I don't use messages, importer and I have never understood why there's a button for the about window. I have set the auto connection so I don't need a button on the toolbar. It would be great to decide what icon is useful and what icon is not. Flexible spaces would also be great but it's secondary.
4) Integration: if I'm downloading a movie, I can see the preview with VLC. But I can't see any preview for other files.
5) File rename don't need to have a button that confirm the action. You change the name in the textfield and it's automatically saved when you close the information window.
6) I don't know if this is a request for the GUI or not, but it's frustrating to see that a file is corrupted/fake because someone is using HyperMule (it sets all the file comments to corrupted/fake). Is it possible to have a filter for the comments?