Note: most of this implied in
my review.
What seems clear: I agree that the boy and girl are both dead at the game's beginning. We are in Limbo, along the fringes of hell. We 'wake up' in the land of the dead estranged from our sister, and try and find our way back to her, crossing the Acheron as we do so. We suffer trials and punishments in Hell, and are eventually reunited with our sister. The main menu screen shows the scene of our death in the 'real' world, where the two children are replaced by the swarms of flies buzzing around their corpses.
What I would speculate: the trials and punishments we suffer are related to the moments, hours, perhaps even the day before death. Some people think that in the upper right of the menu screen you can see a car, and that the children must have died in a car crash. I disagree; I think it's a school bus (when the light moves, you can see it peeping through a row of windows). The siblings were on a school trip. They may have been staying at a hotel in a town or city, and they may have been visiting a factory. Their school bus crashed in the woods. The 'tribe' you meet in the later stages of the woods are the other children who died, and all of the events of the game are warped versions of the last day or so before death. Remember when they roll a flaming tire at you? Yeah.
And when you smash through the glass at the end of the last puzzle, you are reliving the moment just before death, when you smashed through the windshield.