Kings of Israel
The card says "A location containing the most Sin Cubes is destroyed and cannot be entered again..." Does that mean that a prophet can no longer pass through that location?
For example, suppose that Megiddo is destroyed. Can a prophet move from Aphek through Megiddo to Mount Tabor? If so, how many actions would it take? If not, does that mean the prophet now must get from Aphek to Mount Tabor by backtracking to Joppa and then taking either the coast route (Acco) or the inland route (Jabesh Gilead)?
That is correct, the prophets can no longer move through that location. So in your example they would have to backtrack and then take the sea or the East route.