Someone on the hardocp forums pointed out that your city would be online only and it would affect neighbouring cities by other human players, and the knock on effect of this is that you cannot locally save your city.
The age old satisfaction of building up your city and then burning it to the ground with monster attacks, flash floods, riots and fire can no longer be done because it all does permanent damage to your city...reloading isn't an option.
Not only that, but if cities are really affected by their neighbors, then some idiot 10 year old neighbor could get bored and burn his city to the ground and your city would suffer negative repercussions of it. And make no mistake, if that's possible then you'll have a subculture of SC5 players intent just on griefing other players' cities.
In SimCity4 I'd always prefer building on the largest plots. To get the economy of that primary city going, however, I'd create secondary cities in smaller, surrounding plots. Then, when I built up my primary city it benefited from all the workers and jobs of those neighbors. Neighbor cities even allowed your city to be off-balance between R, C, and I.
If SC5 is going to have a similar relationship to it between cities, then a player destroying their city could have some serious effects on yours. And their little demo video kind of alludes to this. If your neighbor was providing you a lot of your workforce or jobs, losing that could absolutely wreck the balance of your own city.
That would just be 100% messed up.