No plot details have been announced. The the villain is understood to be from the comics and not someone written-up for the film. So, if the villain is from the comics and is “a big part of New York,” that likely rules out rumored villains Electro and Carnage, Peter Parker’s professor-turned-reptile the Lizard, or other villainous possibilities Kraven the Hunter, the Vulture and Man-Wolf.
In September 2008, Sam Raimi and Tobey Maguire made deals to direct and star respectively in the fourth and fifth films. Sony wanted to film the sequels together to keep the budget down. In March 2009, Raimi revealed they were just focusing on a fourth film and postponed a fifth.