I have a 2 story and two AC's, whats the best way to set the thermostats?

I have a 2 story (which I am new too), 2 AC units, one for the first floor, one for the second. We only stay on the 1st floor, and only use the 2nd one when we have guests over, which is very seldom. If we like the 1st floor temperature to be 76, whats the best thing energy/electric bill wise to set the 2nd floor thermostat on? Is it better to shut it off completely, keep it the same as the first floor, etc. Thanks for any advice.