The most obvious reason for a karachi plate car to not sell in islamabad is the fact that you get attention from police more often and vice versa. Same rule applies to other cities with some exceptions.
A NWFP registered car is always seen as either non custom paid or involved in some scam. (what police believes). A tampered car is much easier to register in NWFP as compared to lahore, Islamabad.
I heard some guys talking about karachi plate cars, their arguement was that because there is too much humidity (salt as well) in air, cars get rust quickly compared to a car in other city. They gave this reason to knock down the price between 50K to 100K.
The most general trend in every city is to buy the car of same city registered to avoid hassle getting it verified. Other factors include the difference betwen big and small cities, life style and people's behaviour.