If I had to guess, or write a plotline for it (and I wouldn't after what F3ar was) I'd go with a new threat in a whole new place.
Pointman and little brother were projects. Miltary one's. Pretty much weapons, right?
Well, when you make a weapon, you do it to kill something you can't kill with current weapons.
I'd have a new threat appear, the one they were originally made to counter.
Now, to make the story slightly more interesting, I'd have Pointman start with "fuck no" attitude. He doesn't want to be a weapon anymore, he wants to raise the little tyke to be a good boy. So you play the first few levels as Pointman. Then shit gets fucked when the new threat decides it ain't gonna leave him alone.
And he dies.
Yes, I realize most folks wouldn't want to see him die, but honestly, killing an old character is often the best way to make the series move forward with something new.
You'd just have to make sure he dies a badass death and nearly kills the New Threat so it's not a pointless "rock falls, Pointman dies".
Now you play as the little Tyke. He's 16 (technically) doesn't speak and can't act like a normal human being. Which ain't a problem because:
a) 50% of the time is spent on a fucked Earth that is all covered in spooky shit and people are terrified
b)The other 50% of the time you spend on another dimension full of ass-raping creatures.
Ayup, you heard me. The game kinda already touches on extra dimensions and shit. Take that shit up to eleven. Just make a new dimensions where laws of physics are haywire, non-euclidian spaces, walking on walls during combat, all sorts of weird shit and bosses.
Then you constantly pop back in Earth for re-supplies and fending off the ocasional no-lube-ass-rape entity invasion.
Plot points to increase tension (pick 2 or 3, not more else it gets real retarded, real fast):
All in all, you take the Shadow Warrior 2 and put F3ar in it. Heck, even the first one would do without all that extra shit.
Heck, the very first Shadow Warrior was great too and that would work.
I just like Shadow Warrior, why not play that instead?
Because F.E.A.R. was a fucking great game and now the series is dead. FUCK.