When I have to go into the city I usually stay at the Brooklyn Bridge Marriott. The location is across the street from a subway stop on one side and a block or two from a different line out the other side of the hotel. You can get into the Time Square area or lower Manhattan in 10-20mins depending on the hour/day. The property is pretty nice, the staff is very good and there's definitely some cool parts of Brooklyn within a short walk. Unless you really want to walk out of the property and be right in midtown, this one would be my choice. Its also not terribly far from LGA or JFK which makes it a whole lot easier to get to if you are flying into those airports. The one tip I would advise you on, check the city sites and make sure you know when the different bridges are having work done on them. Currently the Brooklyn Bridge has been going through some work, which doesnt impact subways but could limit your ability to walk across it...which is always a great walk :)
All of the above responses recommend great hotels. You should consider where you need to be in Manhattan. Getting around can be time consuming and at times expensive. Find a hotel near most of your activities and then you can just walk there. You mentioned the Marquis which is a great hotel, I was just there a couple of weeks ago. It can be pricey whether you look at dollars or points. If you want to be in the Times Square area, there is a Fairfield, Courtyard and Residence Inn in the south Broadway area.
The Courtyard Times Square South always was the best for me. The Marquis is just too, too much for me. Too large, too crowded and the CY is such a short walk from there. Have a great time! Visit the Duke's (Deli) for an inexpensive, but great, breakfast or lunch! It's in front of the CY on the way to the Marquis.
Jerry has it right on the Marquis. Too many people and waiting for the elevators can take its toll on your spirits. I stayed at the Courtyard 5th Avenue (at 40th) and loved it. It's a block away from the 6th Ave line and two blocks from the Lexington Ave Line.
The Marriott Eastside (at Lexington and 49th) is a great place. The subway is two blocks (on 51st) away; an easy walk to Rockefeller Plaza; two blocks from Madison; close to Grand Central; an easy walk to Times Square. The staff is exceptional and the Concierge Lounge (16th floor) is staffed and very good (also has an outside seating area). We always stay here when visiting NYC. Have fun!
Another vote for the Brooklyn Bridge Marriott here. Make sure you ask for a room in the new tower rather than the old. It is far too noisy on that side. It is within walking distance of the waterfront with some great shops and restaurants along the way. I still miss the fresh hot bagels. :)