Depends on what you want to eat. Harlem has more to offer just soul food. You have Spanish food, African food and everything in between. I personally don't care for the food at Charles' but I'm sure some hounds will be pointing you up that way. It is also off the beaten path so if you have an itinerary of activities that day it would help to point you in the right direction. Here is my perception of places: Sylvia's and Amy Ruth's are very popular destinations for tourists. Spoonbread and Spoonbread Too are cute little places but the food is just okay. Melba's makes wonderful short ribs, has a nice ambiance and is really a spot where the locals eat. MoBay on 125th is another popular spot with good food where the locals like to eat. Baton Rouge (only open 1/2 the week is very expensive for both food and drinks. Copeland's is pretty good and has been around a long time. There is also the little known Margie's Red Rose Diner that just added a dining area. These are just the soul food type places in West Harlem that I can think of off the top of my head. There are also African places and other restaurants in East Harlem.
Check out some of these threads. If you do a search using Harlem or uptown you should get some other suggestions.