Dear outdoors-babe Lisa,
Running / cycling / walking along West Side Highway is one of my favourite things to do, when I'm not being a lazy slob (which is almost always). Go for a run just as the sun is setting, you'll get an amazing view of the Hudson River and the Hoboken (New Jersey) skyline.
My favourite stretch is from Pier 25 (N Moore Street, Tribeca) up to Chelsea Dog Run Park (W 24th Street, Chelsea).