I’m not a big fan of St Mark’s, which has devolved into a sort of theme-park self-parody. However, there are some interesting shops on 9th Street, which runs parallel to St. Mark’s, one block north.
The biggest problem, though, may be mobility. New York is a notoriously wheelchair- and brace-unfriendly place because so many of our buildings are so old. Narrow doorways, small flights of stairs, etc. abound - particularly in the most interesting, less expensive shopping streets. If what you’re interesting is more window-shopping than buying-shopping, though, that’s less of a problem. The uberfabulous, unimaginably expensive stores on Madison Ave in the 60s are gorgeous to look at and fully modernised. But if your budget doesn’t let you drop $5 grand on a handbag, and you want to buy, it may require some ingenuity.
Prince Street, Spring Street and West Broadway in SoHo are all lined with lots of new shops, which are usually accessible. But many of these stores are expensive, or chains that you might have in your home town. (That said, the designs are often really, really cool, worth seeing just for the architecture.) If you can, go on a weekday during the day. Weekends are an absolute madhouse if the weather’s at all tolerable, with almost complete gridlock on the sidewalks. (When I’m not pressed for time, that can actually be kind of fun.)
What sort of things are you looking for?