Well you have to have a limit and there will always be "the most efficient" way to build. It's completely up to you to decide if you want effectiveness or cute prettiness 
I'm sure you could get bigger with plopped buildings, but the actual zoning system seems hard coded to only allow buildings within 4 tiles of a road. You can't zone "deeper" than 4 tiles from a road. This, combined with 4x4 being the default building size, is going to result in a lot of very samey looking cities where everyone makes 8 wide blocks as the default. Building anything other than 8 wide blocks will be pointless. Any smaller and you can't fit 2 rows of buildings, any bigger and you have empty wasted land between.
Why even have zones if you have to plop skyscrapers. So annoying!
I'm sure you could get bigger with plopped buildings, but the actual zoning system seems hard coded to only allow buildings within 4 tiles of a road. You can't zone "deeper" than 4 tiles from a road. This, combined with 4x4 being the default building size, is going to result in a lot of very samey looking cities where everyone makes 8 wide blocks as the default. Building anything other than 8 wide blocks will be pointless. Any smaller and you can't fit 2 rows of buildings, any bigger and you have empty wasted land between.
I assume there will be some growable skyscraper(ish) buildings as well, and that the really large ones that exceed 4x4 need to be plopped. This isn't entirely unrealistic either, in RL projects of that size do usually have the city government involved.