Should I close off the registers (aka diffusers, vents, grills, etc.) in unused areas/rooms in my home?
You should not close too many registers in unused areas because this can cause comfort issues. By closing registers you are restricting the airflow across the heat exchanger, causing the supply air temperature to go up. So you get short blasts of hot air, then the furnace shuts off because the thermostat is satisfied, and then you will begin to feel cold drafts. The system in your home was designed to run with all of your registers open.
The only time you should be closing your registers is if one area gets to be way to hot or cold compared to the rest of your home!