I've driven my motorhome through New York City (well, through a good portion of it) a couple times now. I wouldn't do it unless it was unavoidable, as indeed was the case for me as I was going to camp in Brooklyn at Floyd Bennett Field.
At least at the times I've been through, on the expressways I took, it was hard but not impossible driving. Changing lanes took a little patience and isn't a passive exercise, but people didn't seem to actively try to prevent me from getting where I needed to go. Things move fairly slowly. The pavement is on the rough side. I didn't get to admire the sights much.
I definitely would not recommend it for anyone who's not completely comfortable with driving their RV, who doesn't yet have a quite good intuitive feel for where the limits of the vehicle are both side to side and front to back. I'm sure that the difficulty varies with different days of the week and times of the day, as well. Surface streets are another matter entirely, of course, and many have vehicle or height limitations.
Anyway, if possible, I completely agree with everyone else that it's easiest and wisest to go around New York City rather than through it.