It doesn't really make a difference in terms of performance, reliability ,temperature, noise or anything like that. BUT turning it upside down means you can't accidentally drop anything into the PSU, and it will not gather any dust, and the fixed cables will be closer to the motherboard tray.
I would probably block the front top fan opening, and turn the radiator fans around so they push air out of the case. The bottom fan probably doesn't make any difference since you already have efficient front intake with 2x140mm and you only have one graphics card to cool