Yeah, the mass transportation system could definitely benefit from a district-based approach, both on the basis of currently being unrealistically small, and on the basis of the AI tending to ignore anything except the shortest route meaning that you can add cargo rail terminals all day long and your industrial traffic will *still* head to just one unless you engage in ridiculous micro-management of the traffic flow. If anything, the Industries DLC only made this worse by adding so much extra cargo traffic on the roads. Being able to build *proper* cargo hubs that actually work would be a massive boon.
Other areas that could do with a district expansion are health care and death care - many European hospitals are massive, sprawling affairs, and my local hospital covers at least a couple of square kilometers all on its own, with dozens of buildings, including two huge parking garages, a nursing school, and four pre-schools/kindergartens (one of them is a 24-hour affair for children of the staff, the other three are for kids with disabilities). And tell me you wouldn't love to be able to set up a free form cemetery that could actually handle your whole city properly? For a third area to round out an expansion, you could go with mental health, dealing with stress (caused by noise pollution and overly long commutes).
Someone else I talked to mentioned fire and police services, but I figure fire is already handled by Natural Disasters and police by After Dark, all that could realistically be done with that is adding more prefab buildings in different formats and that's pretty well covered by the workshop. Would be nice to get some more options built into the game for console players, but that doesn't really affect me, and it's not something you could build a whole expansion around.