What the city is best for
Istanbul should be planned by area, travel time and what you actually want to do. It works especially well for city break, culture, food, shopping and history. The main anchors are Hagia Sophia, Topkapı Palace, Grand Bazaar, Bosphorus ferries, Galata Tower and Kadıköy, but the value of the trip depends heavily on where you stay and how you structure the days.
The most useful bases are Sultanahmet for first-time sightseeing, Galata/Karaköy for restaurants and ferries, Kadıköy for local evenings and Nişantaşı/Beşiktaş for shopping and city life. Choose short access to what you will do most, not just the lowest hotel price. For short stays, a better location often saves both time and transport.