I think when season six opens we'll see an alternate timeline in which Oceanic 815 made it safely to Los Angeles on September 22, 2004 but people like Jack Shepherd, Kate Austin, Hugo Reyes and John Locke have spent the last several years feeling as though something is not quite....right. Maybe they have vivid dreams of the island, maybe Hurley has continued to be visited by the ghosts of people he never knew in this timeline such as Libby or Eko. Think something along the line's of TNG's Yesterday's Enterprise. Along the way we will encounter almost every castaway who has died over the course of the series. Charlie, Boone, Shannon, Eko, they're all on the table, we'll see them in this "It's a Wonderful Life
, if you will)" type scenario.
It'll be up to the uniquely special Desmond Hume to repair the timeline.
Or something. I don't know.