TBH, I would love better mouse support(especcially of the 'select retangle kind' for designating instead of the one-square at a time) because I love playing games with my tablet.(Perhaps a little selfish there). For me, it would already be better if we'd be able to click the hot-key explaination as a sort of buttons.
I think though that to be able to effectively redo the DF UI, the game should be rewritten in some parts. Instead of having workshops and rooms from furniture, these would work better if they were similar to the burrows/zones. This is mostly because I really like the idea behind hospitals, even if they're not quite working like they should. Next to that it allows for better workflow when planning things out.
But I think we could also take the things that require 'think hard about it once, and then don't bother with it for a long time' such as nobles and the 'information' screens to the status screen. This way you wouldn't have that kind of clutter on the front-screen, making things easier for newbies to discern.
On the other hand, things like the manager and the military should be readily availeble because these concern mass-orders of some or other.
So combining those two ideas you would get a sort of subdeviding like this:
http://img.ie/bc043.pngAt most, the player would have to tick two keys to get to their needed option, and at the same time the screen is uncluttered.
By placing the 'look' on top, newbies would be most inclined to choose that option, resulting in them being able to figure out what all these symbols mean.(I just realised I forgot to add a few things, like announcements. which should be on the frontscreen but more near hotkeys/status).
And general key-consistency, that would be nice.