In addition to the other listed issues, it's above the altitude at which body temperature causes water to boil, commonly known as the Armstrong Limit. As you may imagine, this significantly complicates cabin depressurization incidents.
> Exposure to pressure below this limit results in a rapid loss of consciousness, followed by a series of changes to cardiovascular and neurological functions, and eventually death, unless pressure is restored within 60–90 seconds.
Climbing that high takes time and fuel. Which you can recover somewhat on descent, but not totally, and under not-ideal circumstances like hiccups in the flight plan the plane even has to waste the potential energy.
I'd say that altitude is the reason for the focus on long distance.
That's what I was thinking, climbing up there burns some fuel, and only so much can be recovered into speed through a slow descent which airliners typically don't do, they hop between Flight Level.
So I suspect only long flights will be operated that high, and there will be some calculation for the optimal altitude for shorter flights.
Getting there … Especially if you are slow, you are causing issues for air traffic control.
Another issue is the survivability of incidents. If something goes wrong, for example with your pressure cabin or your oxygen supply, you have only seconds to start your mitigation measures.
The higher you go, the tighter your flight envelope gets as you approach the "coffin corner" and the more likely you are to stall. A stall is very bad (you lose lift and fall out of the sky).
Stalls are very bad when the aircraft is close to the ground. Stalls at about 5000 feet or more above ground level can be recovered from reliably by professional pilots, which is why (combined with the existence of autopilots and the fact that it is the cheapest way to cover distance) the majority of the thousands of airliners in the sky right now are right up against the coffin corner.
As long as you know you're stalling. Air France 447 stalled all the way from cruising to crashing into the Atlantic without anyone onboard realizing it.
