I would always have the drive the right way up. This is the best dynamic for the platter and the heads, it is very important that the heads do not contact the platter surface (when the platters are rotating).
Even when the drive is on the side there will be difference in the speed fo the platters on the up side as on the down side. These may be small, but timing is everything!!!
As for the drive being upsidedown NO, this is not the way the head are desingened to opperate.