I'm willing to bet that changing the look (not functionality) of the interface is one of the easier mods.
What might be cool (if we still had formal ages) would be to have the interface change styles as you progressed through the game. To take it to another level, the interface could have a per-civ/ethnicity appearance. The interface you saw playing as China would be different from the interface for Mali. To take it even further, maybe the whole interface doesn't change at once, but rather as you progress through the various different tracks. If you have many military techs and few economic ones, your military screens would be more modern than your economic ones. Finally, you could even make parts of the interface dependent on your civics choices. If you're a communist police state, the interface could be in black and grey and red. If you're environmental pacifist, it could be soothing greens and blues. Or it could depend on the state of things in the game. If you're at war, it's red. If you're at peace, it's blue. If you've just gotten a great person or some other momentous event, it could glow warmly. If you're trailing behind the other civs, the colors could be muted and dull. This could even extend to the appearance of the terrain and units and cities. There's lots of potential for tweaking the interface to reflect things happening in the game to give another channel for the player to "feel" what's going on. You wouldn't have to be a graphic artist and a programmer to enable this, either; there's an opportunity here for a programmer to create a reusable framework that multiple graphic artists could plug images into. It could be like skinning Winamp, but much, much more interesting.