Large cities really should be very dangerous. Filled with zombies of all kinds. I liked being nervous about going to them, that's what a horror game should do.
I hope when the radiation zones become traversable we get a real end-game area. Or at least add to every Random Gen a extra large centre city like the old cities located in a large wasteland with random radiation patches (to add to the danger) that has the green death and rainy atmosphere. I think atmosphere is really important to a game like this and I like the feeling of foreboding that the cities used to have.
Now they are just free loot zones. You should have to build up to savaging cities. Starting at small towns, then going to large towns, then small cities, then large cities, then radiation cities. The last three being filled to ♥♥♥♥ with death!
Cities and towns are now empty, sleepers alone just offer no challenge, as long as you sneak. You can clear out even the largest building no problem.
A centre hub city (I think) is a good idea. Sewers/sub-ways, car-parks and danger. I also like that centre cities looked like cities in regard to pavements (sidewalks) and random ruined buildings. I wouldn't mind being able to hand craft centre hub cities which spawn in the middle of the map. The city design picked being random. Maybe add a workshop kind of thing where people can craft a city in a flatworld and can be submitted and the Fun Pimps (if they think it's good enough) can add it to the game. I imagine you would start with a base (streets/roads) already crafted and the wasteland that it stands on already there too. A template if you will.
I would love to be able to craft a city with an underground system of sewers and subways and a hand-crafted feel that people can explore in their world, or whatever city happens to be picked to be in the centre, handcrafted or otherwise.