Might be a lack of oxygen, similar to Helios Airways 522?

http://en.wikipedia.org/wiki/Helios_Airways_Flight_522

That doesn't really explain the dramatic change in course. To essentially do a 180 degree turn and fly the opposite direction there must have been some sort of pilot input into the navigational system.

It's amazing how stupid people can be when oxygen deprived. My dad had decompression chamber training with the Aussie air force. They gave everyone a clipboard questionnaire with some simple puzzles. In oxygen-deprived state most people were writing off the edge of the clipboard and on their legs.

True, but it doesn't really fit with disabling the transponders and changing course moments after communicating normally with ATC.

Any theory other than deliberate action seems to rely on several major coincidences. Not strictly impossible, but definitely not the most plausible option.

Agreed, what does this aircraft do when the FMS has no more waypoints to head towards? What if the wrong waypoint was fat-fingered?

Pilot suicide has happened before. Some of what happened, such as possibly ascending to a high altitude early in the flight is consistent with a pilot incapacitating the passengers and the rest of the crew, and maybe himself, too, by outlasting the emergency oxygen. If the pilot intended to conceal evidence of what happened, setting a course to a very remote part of the ocean would be consistent with that goal.