Ok, good question. If the valve is upside down, there is a large probability of damage. Also if there is a damage, leak etc. from the first stage or valve, it is almost impossible to notice, feel or hear it. Probably you notice it when the hose goes tight. Not fun.
There have also been many divers who have sat on, knocked and countless other blunders to their tanks when inverted, and lets face it, equipment is not cheap.
If you are having trouble reaching the valve for your tank, then the tank is not positioned properly. If you have the tank as high as it can go then there might be an issue with the type of bcd you are using and it may not allow you to position it properly.
If you use a plate/harness usually there is no issues what so ever, and in the unlikely event that you are in a position where it is difficult, you loosen the belt buckle on the harness to all you to push up the plate/harness to reach the valve.
Also your hands should always be in a position where you can see the computer on your right hand, compass on the left, and access your spg clipped off on the waist d ring. reaching over your shoulder and behind your neck to do gas shut off or to isolate a tank is very very easy and accessible. Having the valves below and behind in a tight spot can leave you in a position to not have any way to do a shutdown, and the obvious result of that is scary. If your hands are always in a position to reach the valves below you then how do you look at your gauges? You can't. How do you adjust the buoyancy for the bcd and dry suit? you can't. With your hands and valves in the forward position you have easy access to everything you need.
I hope this helps.