6th Avenue will be closed for a street fair during the day 11am to 6pm whatever the usual routine is for street fairs. And so that may clog the arteries going uptown and crosstown all around the West Village, Chelsea, and will make the trips long and frustrating. Until about 4pm, 10th Avenue should be good, so if you have to be west, go far, far west. Once the fireworks come, stay on the east side of Manhattan, which is pretty much a good idea always.
Water Street will be closed between Fulton and Broad Streets as well from 11am to 6pm
Also check the DOT web page, it differs on how much of the West Side Highway and 12th avenue will be closed.
6th Avenue will be closed from 42nd to 56th. Madison may be the best bet.
Lexington Ave will be closed from 42nd to 34th.