How does many people having played the instrument affect its playability? Production guitars are not the most consistent things around, so a new piece in a box might actually be inferior to the one on display and vice versa.
Common sense dictates most things. Check for manufacturing defects, i.e cracks, warped necks etc. There's no guarantee a new guitar in a box won't have these problems.
I don't know about you guys, but I will never buy a guitar unplayed, not even another piece of the same model.