Artwork need not just be a Van Gogh in your bedroom. If you are looking for something older, something with a bit of history on it, then check out Pageant in the East Village.
Established in 1946, Pageant has had several homes including several locations along Fourth Avenue, known as Book Row of America, and was of *seminal* importance in Woody Allen's "Hannah and Her Sisters" where Michael Caine and Barbara Hershey went browsing for a copy of e.e. cumming's poems.
It's worth noting that the Caine/Hershey scene in Hannah and Her Sisters was *not* filmed at Pageant's present store but rather at its (original?) location on 9th St. between Broadway and 4th Ave. The store moved to Houston St. in the mid '90s, and then again to its current 4th St. location.
Between Fourth and Third avenues, actually. The location became a restaurant, also called Pagent, and is now a Irish pub. As for Pagent itself, it's morphed from a book shop with prints to a print shop with books and was (the last time I dealt with anyone there over a decade ago) one of the few bookshops in the city that went on to a second generation of ownership in the same family. I hesitate to disagree with anything Maxwell says, but I don't share his enthusiasm for the establishment.