Hi,
Sorry to butt in so late in the discussion, but as somebody who has to think about UI design professionally I wanted to weigh in on the whole issue.
First off, yes the aMule GUI is horrible. The non-nativity does play an important role (Mac user here), but there are simply of lot of really bad UI design choices being made as well. For starters, let's compare aMule to another app, Transmission.

In these screenshots, both are doing the same thing: downloading stuff and presenting details about one download. Transmission does so using about 2.5 times less screen real estate. Here a direct comparison:

If you go through the details of what information is available in both apps, you'll find that both present very much the same level of detail about what's going on. Transmission actually gives more information: Every currently active download + details about a selected one, while aMule only manages to squeeze one download + details about it into the same space. Lots of clunkyness and wasted real estate on aMule's part here.

More of it on the network tab. Why two ED2k/Kad tabs? Why a huge, pretty useless graph on the Kad tab? The actually usable part of the Kad tab is so tiny, it could easily be put next to the server list. Why a separate ED2k Info/Server Info/Kad Info, all of which contain lots of free space (and the server info mostly spam messages)? The log would be entirely unnecessary for 95% of the users, if the other three tabs would present the contained information in a more orderly fashion. After all, the only purpose of these tabs is to let the user know whether he's connected or not, plus a few statistical details. But as it is, the information is all over the place in tiny bits and pieces, plus partially redundant in the status bar at the bottom.
Then there are the real usability issues like Global vs. Kad search. If I want to make sure I got every possible search result, I have to perform two searches. That's something the computer should do for me. Where's the "Search everywhere" option?
What struck me most in this thread is the hostility and ignorance of (some) of the main developers towards GUIs. I agree that users should familiarize themselves with the tools they're using, but that does not mean that everyone CAN do that. Fact is that aMule lives of the people using it (the ed2k network). Another fact is that only a tiny percentage of users will ever fully understand how it works. That's mainly you guys and a handful of technically minded people. If 90% of your users need a manual or and explanation for every other thing in the GUI, maybe it's just a bad GUI. If you don't get this, you shouldn't make GUIs. If aMule would be my creation, I'd take some more pride in my work and make sure it's as polished as possible. Sending people away with "If you don't get it, don't use it" is simply a lazy answer. Also, I do GET aMule. I'd love to use it more. I was a big eMule fan back when I had the luxury of a dedicated Windows machine in my old apartment. But now I just avoid using it unless absolutely necessary, because it's mainly a pain in the butt.
You first need to realize that you have a problem... Seeing the "official" reactions I think aMule will unfortunately continue to be a mediocre app.
Best Regards.
EDIT: Forgot to rebut a common rebuttal in this thread: making a better UI doesn't mean dumbing it down. A GUI can be more usable, even for "novices", without loosing functionality or information! It's a matter of striking the right balance.