Before I get into why I believe Dr. Halsey will die in Halo 5, here are some of the main characters who have died in previous Halo games:
Halo: CE- Captain Keys
Halo 2- Tartarus, Prophet of Regret, Prophet of Mercy
Halo 3- Sergeant Johnson, Miranda Keys, Prophet of Truth, 343 Guilty Spark, Gravemind(?)
Halo Wars- Arbiter Ripa 'Moramee, Sergeant Forge
Halo: Reach- Carter, Kat, Emile, Jorge, Noble 6.
Halo 4- Cortana, Ur Didact (presumably).
So what we basically know is that 343i (and Bungie) aren’t afraid to kill off main characters, and usually kill a few each game. So, if I had to pick one I’d go with Dr Halsey.
This is because she is old and frail, she only has one arm (which is possibly infected), she is hit-listed by the UNSC (and ONI), she is arguably now an antagonist, and her desire for knowledge usually puts her in bad situations.
Also, if the Janus key parts are joined up again and all the Forerunner secrets and locations are finally revealed, than her character may no longer be too relevant for the series.
Also, if Cortana comes back to life, I think we’ll definitely see the end of Halsey- simply because they’re too similar, and there would be no need for both of them in the games.
(If I had to pick a second character, I’d go with an antagonist, most likely Jul 'Mdama, or ONI’s Serin Osman).
Who do you think & why?