• Star Junction, Rockstar's version of Times Square, is very lively. Pedestrians are more realistic, performing various activities like smoking, reading, eating, or dialing phones while not paying attention.
• Cabs can take you anywhere, call them anytime by whistling.
• Every street has a name.
• Internet can be accessed from any working computer. Browse various sites, use online dating services, and even send resumes online.
• After sending a resume, it normally takes some time before getting a response (must be one of the time specific missions Rockstar was talking about).
• Missions will require some investigative elements.
• Shooting people is more realistic, matching the game's look.
• Cops have a circular area of given radius depending on the severity of the crime, must get outside radius to remove wanted stars.
• When found by the cops, the circle re-centers on your location.
• Clothes available for purchase are more grounded and more realistic.
• Free aiming will allow you to shoot anywhere while in third-person.
• New system allows you to take cover behind "anything that would make sense" during shootouts, but most covers are easily destructible.
• No more Ammunation. Guns can be purchased from guns dealer named Little Jacob who's driving around with a packed trunk.
  
• Phone lets you check your email, keep a list of contacts, take pictures with its camera, and remind you of events via calendar.
• Making calls will help a lot in making relationships, playing a part in determining who will work for you.
• No more heart containers, food and rest will be the only means of health recovery.
• Map has GPS tracking, shows the quickest route to get to target destination.
• Camera, both on-foot or while driving, is tighter to allow you to see straight ahead a little more.
• Current soundtrack will blow you away, but licensing issues might do some changes.

Via IGN