In Manhattan the low zones are due to the soil not being good for higher construction. Lower Manhattan and midtown are made of basalt stone that is extremely strong and apt for skyscrapers.
So that 2.5x square footage is more like 1.5x when it comes to the number of units of like quality/liveability you can pack in.
As a result, Midtown is now one of the few places in New York's metropolitan that can reach the millions of people in the five boroughs and the suburbs all at once, which means the labor market is substantially larger than what it is in Lower Manhattan or Downtown Brooklyn, and makes it massively more attractive for employers.