Offline singleplayer is a must (and I'm pretty sure we'll get that, considering how much backlash there is when we don't) but some sort of multiplayer component would be welcome, too.
I know, it's weird to ask for the very feature that brought down EA's SimCity in 2013, but I don't think I'm alone in wanting some sort of multiplayer component in Cities: Skylines 2-provided it's optional for players.