Some of it depends on just how open the floor plan is. Any setback helps, but more is typical. Some of the thermostats are smarter than others. Most of the Honeywells (and maybe some others), you set the time you want the house a certain temp, and it learns how fast it cooled off and how fast it can warm up. Then, it may turn on 15-minutes early on a mild day, or an hour early on a nasty one.
It also depends somewhat on the size of the furnaces...from a comfort standpoint, running one continouosly makes for the most comfort. I'd think about that, and use the second as a backup if it is needed on a cold day, but you'll have heat distribution issues since the second story isn't being fed by the duct system, and the coverage may be uneven, especially if you close doors.