Does keeping downstairs air off at night force the upstairs hvac to work harder?
Let's change our nomenclature around to say your house has two zones and each zone has two states, occupied and unoccupied. Being able to adjust each zone so that it is only running while occupied is exactly what you are trying to achieve in Building Management System because there could be substantial savings to be gained.  

This is just a fancy way of telling you that you are doing the right thing. If you're thinking about leaving them both on to compensate for warm air, it is not generally considered better than having them set as you originally stated. In my opinion, the important part would be to have your zone set at 80 to come on and cool down just before dawn during the cool part of the day rather to have it come on and try to cool when outside temperature is at say 100 and rising. 

I don't think anyone can really put a fine point on this. Since there are a lot of factors to consider while trying to get the best efficiency from your system. It would be quite hard without a survey of your residence.