My 2c:
There was a failed hijacking (possibly to divert the plane to another location), and the pilots are both killed or disabled in the scuffle.
The plane might have gone to 45K during the fight.
The planes returns to normal altitude on autopilot, but none of the passengers know how to fly the plane.
They can't figure out the radio - or it's broken during the hijacking. It's night, so they can't see where they are, and just keep going until it's daytime and they can see some place to try to land. When day breaks, they're way out over the ocean, and out of fuel.
Or aliens, both are about as probable..