There's no crosstown subway lines north of Central Park, just the ones that run north/south under the avenues. It would be preferable to see a cross town line be built, probably at 116th or 125th street, before massively building up the Harlem area. Personally, I think that 125th street would be best, because it's a wide street like 57th, 42nd or 34th, so it's already something of a focus of activity, and it would tie in with the 125th street MetroNorth commuter rail station. The under construction 2nd avenue subway line will have a spur onto 125th street, so it shouldn't be too hard in the future to extend it further west across the island. Once that's done, the several blocks north and south of 125th could be massively up zoned like the Hudson Yards, and another supertall row could be developed.
Of course I haven't seen a plan this ambitious being seriously considered by the city, and it's not really worth considering, until the WTC and Hudson Yards are built out. By the Yards, I mean not just the yards themselves and the boulevard, but also redeveloping the Javitts Convention Center, and the blocks south of the yards, which are equally underutilized, but haven't been rezoned yet. Infrastructure wise, a 125th street subway wouldn't be built until after the second ave line is completed, and at the rate it's going, its not going to be fully funded never mind built for another couple decades.
As for northern Manhattan looking different than the rest of the island, that's partly because of the geology of the island, and partly because of how it was developed. The northern end is much hillier, with occasional steep cliffs which mirror the Palisades in New Jersey. The rugged terrain made it harder to maintain the street grid when the streets were laid out. As for the development pattern, that's because development started at the southern tip, and grew northwards. The chaotic jumble of streets in the southern financial district is from the colonial era, before the city was formally planned. Moving north into tribeca, soho, smaller sections of grid start emerging, as entire areas were being planned and developed in a haphazard manner. In 1811, the city adopted a new master plan that stopped the piecemeal development and established the present grid, allowing development to march orderly northward. At first, the plots marked out by the surveyors were rather narrow, resulting in the common tenement. Over time, the grid has been broken up by public housing projects and co-ops, and developers have built bigger towers by assembling the small tenement lots into larger plots.
There's a variety of reasons way Harlem hasn't been developed as intensely as Midtown or the financial district. The density of development was influenced by the transportation infrastructure (Before 1961, developers had free reign to build however big they wanted, so zoning wasn't an issue). At first, the subways (first built as elevated lines) were built for commuting between the predominantly residential neighborhoods that were growing steadily northward, and the southern financial district(wall street), and the industrial area directly north of that(docks, meatpacking district, garment district, newspaper row, etc). These lines were only for local transportation though. When New York Central RR and Pennsylvania Central RR wanted to build terminals for their interstate rail lines, the city had already forbidden steam powered trains south of 42nd street, so that's where New York Central built Grand Central Station. What would eventually become the Mid town business district grew around the terminal. Penn Central didn't want to be left with out a Manhattan terminal though. Since the tunnel under the Hudson required that they use electric trains anyway, the steam prohibition below 42nd street was not an issue, and they had more flexibility locating the station. Land near the financial district would have been too expensive, as would land directly adjacent to the NY Grand Central Station, so they split the difference by building Penn Station several blocks south of Grand Central, where the land was still cheap. Northern Manhattan never got a rail terminal to act as a an anchor for intense commercial development like Midtown did, so it stayed mostly lowrise residential well into the mid 20th century. By then, economic issues like white flight and redlining led to urban decay in Northern Manhattan (which isn't to say that other parts of the city weren't seeing their share of decay too). In 1961, NY adopted zoning regulations which for the first time limited the maximum bulk allowed to be built. This effectively locked in the existing development patterns, ensuring that it would be focused around downtown and midtown, and disallowing major projects except for the public housing projects I mentioned earlier else where.
http://en.wikipedia.org/wiki/Second_Avenue_Subway
http://en.wikipedia.org/wiki/125th_Street_(Manhattan)
http://en.wikipedia.org/wiki/The_Palisades_(Hudson_River)
http://en.wikipedia.org/wiki/Commissioners%27_Plan_of_1811
http://en.wikipedia.org/wiki/Upper_Manhattan
http://en.wikipedia.org/wiki/White_flight
http://en.wikipedia.org/wiki/Redlining
http://www.worldcat.org/title/seeing-red...rlem/oclc/18759575?referer=brief_results
Oh dear, this post ended up rather long.