They need to make sure UC4 starts a bit different due to how UC3 ended.
Drake has given up his obsession with treasure hunting.
The stakes need to be high in order to get him back on track for us to enjoy yet another journey. Otherwise it will feel like our previous adventure and journey didn't matter which would be awful.
Whatever ND does:
I hope Charlie Cutter plays a big role and is the man who is responsible of the "treasure hunt".
Whenever Chloe wanted to stop, Charlie was the person who kept pushing Drake to continue.
Chloe: "It just isnt worth it Drake, Let this one go."
Charlie: "No no no no, you can't just give up. If you let these **bleep** win.. After this! I will never bloody forgive ya."
I can see Drake being there for HIM in order to "repay" the favour so to speak (and them being friends and all).
Uncharted 4 NEEDS this in order to feel authentic to what Uncharted 3 did.
We need to know more about Charlie Cutter and this is the perfect way to go about it. Make a story around Cutter and have Drake (the player), be there for him.