Ultimately, the show is about human reaction to fate. There is no creator that decides this fate, and people living thru this fate nearly always feel like they have a choice. Locke represents the mistaken belief in some creator of fate, and Jack is the refusal to accept fate at any level. Desmond is the alternative, by his refusal to accept the argument made at the Lighthouse that he must go back to the island, and his decision to go live a good life with Penny. Desmond's response will be shown to be the most rational and fulfilling by the end of the show.
The season 5 finale was a microcosm of the whole show, with Rose & Bernard fulfilling the role of Desmond. In that episode, we are basically splitting time equally between two stories.
One, we are led to believe, is about Locke finally discovering his grand purpose. All this belief, destiny, guidance from the island, being special stuff that we've been led to think about Locke is coming to fruition. And then it turns out to be completely false, as he is already dead.
In the other story, Jack thinks he can fix everything. That's who the guy has been for the entire show, and now it's his ultimate opportunity. The story follows his effort to erase the entire plane crash, and who knows what else. He will fail also, as whatever happens, happened.
So the episode's two main story arcs demonstrate human ways of dealing with fate that ultimately fail. And yet, there is also the return one-off of Rose & Bernard, who tell our Losties just to "live in the moment" and enjoy life and the people you are with. The show will end up demonstrating that despite all this craziness on the island, the show is really about the people like Damon & Carlton said, and folks like Desmond and Rose & Bernard will be shown to be the wisest of all.
All the mysteries of the island are there to serve this larger human story and existential question. But all these mysteries stem from the strange physics of the island due to the energy deep below. Nothing in the show is supernatural, but those kinds of thoughts always arise when we fail to possess the scientific understanding of the natural world. And the show intentionally plays off of that part of human nature to keep us guessing. MIB/Smokey is like Dr Manhattan from the Watchmen except stuck on the island, Jacob & Richard don't age for the same reason Sawyer and the other time travelers don't age when they time travel, Jacob used religion to keep the Others in his service but it was all a lie, premonitions & flashes are due to the human mind not being completely wedded to the linear notion of time, there is no course correction but simply mistaken premonitions, and pregnancies fail on the island after 1977 because time is no longer moving at a normal rate and women/! men and their reproductive organs/fetuses no longer age at the same rate.