If you live in Manhattan south of 60th, your number one transit option should almost never be driving a car.
I'm talking about from the Seaport all the way up to Alphabet City. I hope you've got strong legs.
Tangentially, this is one of the reasons that nearly-invisible corners of Manhattan like the eastern end of Cherry St and Water St still have serious crime problems today.
Honestly that whole stretch between Smith Houses and Vladeck Houses is pretty fucked.