What is the best physical location for a home thermostat. Does it matter that it is near a cold air return?

Definitely not near the cold air return for starters. Usually a good place would be not near a register of any kind and not where it would be near an entry door either.

according to how your home is laid out,,if possible somewhere close to center of house,in a room that is most used and on a inside wall,not attached to an outside wall,,I`ve found its much better to be atleast 10 feet away from return but better to be close to the return than be close to a supply vent