When are you going? Today was tshirt weather, last week there was a snow flurry, it's that changeable at the mo. By December onwards, it's normally freezing, especially with the wind howling down the avenues.
How long are you going for and what is it you want from the experience? Personally, I think everyone on their first trip to NYC should kind of put the shopping on the backburner (ie buy stuff if you see it, but don't waste hours trying to find several particular stores that dotted all over the city).
The Upper East Side and Midtown have all the famed high end department stores. Personally, I hate Macy's and am not a big fan of Burlington Coat Factory - that place sells falls apart seconds and smells really weird, wherever you go to it!
For purses and handbags, there are all the big names in all the department stores, and they all have their own flagship stores. However, if you go to Canal Street, you can get really soft leather knock offs for as little as $20. Buy 10 of them in every colour! Then head down to Chinatown for Dim Sum and soup.
Other than that, research what you want to do and just do that. Walk as much as you can to get a feel for the city. Get a rickshaw ride as they are crazily fun (and just the right side of dangerous). Each area has it's own unique thing to offer, so you should just find out where you think you would fit. I like the UES to grab lunch or coffee and plastic surgery people watch. I like the UWS as that is where I would live if I didn't have to live in the suburbs. I like the LES as it's a bit grimy and there are great restaurants. I like the Meatpackers as I like to party. I like SoHo as its funky and the shopping is quite contained. Etc etc!
I just think NYC is so many different things to so many people that you need to work out what it is that you want from it. And, if you want easy shopping in one location that can be done in a small amount of time (for less money), I would just get a train to the mall in Jersey City or White Plains or Paramus and do all the shopping in one place, in a very small amount of time, and then go back to the city and enjoy it.
Sorry, this was a longer essay than I was planning!!