I love how eclectic the scene is downtown - there will be a restaurant next to a leather store next to a tea house, and the street will look pristine.
Most of the time, different shifts of people occupy the street. The early birds walk their dogs, and get the paper and coffee on the corner. After the morning rush hour, the clothing stores open. Restaurants serve lunch. People from outside the neighborhood come in for dinner and drinks.
The main streets are active between 6 am and 2 am, but in case you're out any later, you can count on delis and newsstands that are open all night.
Incidentally it's these different shifts of foot traffic that ensures a neighborhood's safety. If there are witnesses, there is little chance of crime.
Related posts: Riding in Style in the Village, Down in the Village and On Street Corners in the East Village.