First post, so sorry if it is already discussed somewhere else.
1) Script API. This could make life much easier for newbies since they could just grab a specific helper program (or set of), and more experianced users could write up their own programs to help them out with a specific job (say, repeatedly proccessing quarry bush leaves or brewing alcohol). One idea for implementation would be that each script would require a dwarf to execute (kind of like replacing their default AI with a user-written one).
1a) Use Lua for the scripting language. Their website gives plenty of reasons why, and other projects (Vendetta Online and Awesome Window Manager come to mind) have used it to great effect.
2) User-definable UI. The idea of making the menu system a little more intuitive has been passed around I'm sure, and giving the user (some) control over the UI can also help cover edge cases where a standard GUI might fail.
2a) Expanded hotkeys would fit under this heading, and defining hotkeys for some task (mass dumping) could save keystrokes and allow players to spend less time paused and more time watching their dwarves.
For a much more complex (and probably much more flexible) suggestion:
3) Seperate the game core and the UI entirely. Using a client/server model should allow for a plethora of new interfaces, such as 3D, graphic 2d (isometric), and framebuffer in Linux (I havn't seen the frame buffer driver listed in the init.txt file work).