Woo, first post. Anyway, I've begun work on a new layout for WordPress' back end (wp-admin) that, at least in my personal opinion, is much nicer to use than the current design. Here's a screenshot of what it looks like and here's a preliminary jab at the post page. (Just a note: this is all CSS so far, but there are some PHP code changes I'd like to make to edit-form.php.)
Even if, say, the main WP developer (whoever you are...*waves*) doesn't decide to accept this exact style sheet (obviously it's too colorful and serif-less :-D), there is one key change that I think the WordPress GUI would benefit from. WordPress desperately needs a permanent sidebar. It may seem clichÃ©, but sidebars truly reduce clutter; for example, placing all "advanced editing" options on post.php's sidebar would remove the need for an advanced editing mode.
One other little thing I'd like to see is a large title input box on the post/edit page. It's always seemed that one of the most important attributes of a post has received far too little emphasis.