For maximum efficiency in regions, should I start a medium city or a small city?
Well, I always start out on a medium map for more space. Usually you build up your one colony and it has all of the buildings it needs to grow on that one map at first. But then once you start growing, you'll end up delegating different responsibilities to other maps and building tons of the same kind of buildings on them so that each map is specialized, which means you'll be able to start deleting things on your original map, so you could start off with a small map as well because of that.
Usually what I do to the original starter map once I've delegated almost everything else to other maps is turn it into a Capital, with government, commercial, and tourist buildings covering the map, so I want a medium size map in order to add absolutely tons of tourism.
The region is 50*50 anyway so that's 2500 small maps and 576 mediums, so you won't run out of space