We don't use the second story of our home. Is it better to shut off the air conditioning completely upstairs to save money, or keep it set but at a higher temperature, such as 78-80 °F?
Almost certainly you should shut off the upstairs AC completely. Ideally you would also seal off the second floor as much as by shutting a door at the top or bottom of the stairs (or installing a curtain across it or something).
The only reasons I can think of to leave it on would be:
I don't know about closing off the second floor. Depending on your climate it could possibly get to over 100 degrees if it is totally closed off - and possibly well above that. It could also get really humid.
And I doubt you have insulation between the two floors. So not only with the temperature changes are you rolling the dice with drywall cracking, door/trim issues, hardwood floor issues if you have them, and issues with tile... but you could also have issues on the first floor in the ceiling area.
It really depends on the climate and what you have upstairs if you are willing to chance a couple of cracks in your drywall. I would leave it around 80.