I think if one of "the main 4" dies it has to be end game. If you primarily control Noctis, and a lot of his big moves are combos with the other members, then by killing one of them you effectively remove a fourth of Noctis' skill set. Out of all the awesome guest characters revealed, there's been no indication that one of them will replace the stats of a pre-existing party member.

But with that in mind, the journey won't be without sadness or loss. Kingsglaive and the trailer reveals for the game do a good job of showing struggle and life threatening situations.