When I went last, in 2005, I was sent to the Meat Packing District... I was dubious because of the name... But it was a very good night out... I had sex 6 hours after I'd landed in NY with a beautiful lady.... So it was a succesful night...
Then there's all the obvious sights.... Empire State Building, Statue of Liberty....
Definately factor in Ground Zero... It's a huge part of modern history and was very eerie when I went. Me and my mates just stood in silence for about 20 minutes.