The writers told us the story about "The Constant", "Flashes Before Your Eyes", and Desmond's mind travel for a reason. The reason is so we have at least a frame of reference when this happens to Jack, Sawyer, Kate, Hurley, Miles and everyone who blew up and died thanks to Jughead.
That's right, take those two episodes and you essentially have backdrop to season 6. I'll Explain.
Bare with me here. Remember Flashes Before Your Eyes - Des wants the ring, Hawking stops him, he breaks it off with Pen, he gets to the island eventually. Remember the Constant - Des is mind traveling, but still remembers the island. He remembers both even in the past. It's fuzzy, but he knows something is going on.
Well now apply that to Jack and company who have just came in contact with the same flash stuff from the Hatch as did Desmond. If it had some effect on him than it's safe to say that it will happen to them too.
My prediction is that when season 6 begins we will see something reminiscent of what you would expect from one of the Final Destination movies. Probably Jack, who always has to fix everything, will try to stop the plane from flying into a certain area. Maybe we will finally find out why the plane was 1000 miles of course in the 1st place. Difference here is that there will be no Mrs. Hawking to prevent it. From there, the universe will course correct, but it will take time.
We are going to have to see our Losties living lives they were never "meant" to live from the point the plane lands at LAX, until they somehow all end up back at the island during the time of the Flight 316 crash. This means that John Locke will arrive at the island in a wheelchair, rather than in a coffin. Interesting.