In tight spaces, you will find more opinions, not less, with a smaller layout - I presume HO. Why? Well in a large layout you can pretty much do what you want, in a small layout there are going to be compromises. So I always answer your type of question with what would give me a great deal of pleasure, but I come with assumptions:
1) A good layout entails lots of switching and continuous running isn't important.
2) I can incorporate other RR lines.
3) There is some form of staging.
4) There is potential for great visuals.
5) I can have "reasonable" curves - 30 inches.
So I would build a U shaped layout that is a harbour switching layout, probably based loosely on the harbour area here in Vancouver BC. In a very short distance, BNSF and CN and CP all operate. There is a working rail barge that BNSF uses (great for staging cars on and of the layout). There are three universals that allow you to bring in just about any type of cars and they are 1) ports 2) bulk transfer areas (modern team track) and 3) interchange tracks. Your (my) layout would have all three so you could virtually switch any type of cars you wished.
The tall buildings would constitute your "urban" valleys, so large tall sugar refinery with giant wheat pools, etc would give you your mountains and valleys.
With a U shaped layout you could have your decks about 28 inches wide, giving you an ailse of 3 foot 8 inches. Your layout could easily handle three operators standing stastic but passing trains off to the next operator.
Just one idea.