Will this be the first Halo game where...

…you fight humans?
I know it’s been suggested they will show signs of evilness (for lack of a better word), but I mean actually fighting/killing Marines and ODST (etc.).

I can see it happening in the final or second last level: Arbie and Locke are escaping the confines of the UNSC/ONI and need to fight to escape.
Or the Chief is betrayed by the UNSC for helping Dr. Halsey.

What do you guys think, how might this tie into your campaign theories?

I highly doubt that the Chief or Agent Locke will ever turn their back on the UNSC/ONI.

Insurrectionists? Maybe. But Actual fellow Soldiers? Very unlikely. Chief may be discovering his humanity once more. But judging by 343’s plans for him (The Heroes Journey), It’s very likely he shall return in Halo 6 as the Hero that Humanity needs. Basically, He’s going to resolve the problems with Humanity so they can advance to uphold the Mantle of Responsibility.

I fail to see how Chief could do that if hes busy Tea-Bagging fellow Soldiers…

I’m not entirely sure about fighting ONI/UNSC directly.

While ONI certainly has some antagonistic traits as of late that Chief wouldn’t be very happy with, they’re still an intelligence agency. They have ONI Security agents, but that’s about it for personal defense.

What could being humans into the Chief’s (or another character) scope, at least for part of the game, would be the Insurrectionists. The New Colonial Alliance has been popping up in Escalations and such, and they seem to be a rising threat.