Story: As for the story, you could use the first game as inspiration, but I think the more recent 3rd game Drake's Deception might be better, as we get an origin of how Drake met Sully, as well as a slight origin of drake himself.
Uncharted 3 sees protagonist Nathan Drake and mentor Victor Sullivan traveling around the world to such places as the Rub' al Khali desert, in search of the legendary lost city, the Iram of the Pillars. Elena Fisher and Chloe Frazer also return in Uncharted 3. The plot draws from the archaeology days of T. E. Lawrence.
The Cast
Nathan "Nate" Drake (Joel Edgerton)
I could of easily chosen fan favourite Nathan Fillion to fill the role, but Fillion is a little bit too old for the role of a late 20's, early 30's. while Edgerton is only 4 years younger then Fillion, i think he would do a great job at bringing the seriousness nature of Nathan out, as well has his joking, han solo-esque charm.
Victor "Sully" Sullivan ( Bruce Campbell)
With Sully, I decided to go with the fan favourite, Bruce Campbell. Bruce is the best actor suited for bringing out the father figure in Victor, as well as his famous joking side.
Elena Fisher (Janurary Jones)
Janurary Jones was my only pick for Elena Fisher, American journalist, TV personality and Foriegn Correspondant. I think Jones could pull of Elena's young and naive personality, while growing into a more cynical hesitant person.
Chloe Frazer ( Claudia Black)
This is a no-brainer, getting Claudia to play her character live action is perfect. Claudia is well suited for action roles, as she has been in Stargate and Farscape, among others.
Charlie Cutter (Jason Statham)
Satham basically is Cutter, a hard Brit ( who is claustrophobic) they even look very similar.
Katherine Marlowe (Hellen Mirren or Glenn Close)
I couldn't decide which Actress i wanted to play baddie Katherine Marlowe, Mirren is a very accomplished actress and would be very suited for the role. the same can be said for Glenn Close. both would offer a lot to this character.
Talbot (Bradley Cooper)
Marlowes right hand man, Cooper would be very suited for this bad guy role, this guy is basically a polar opposite of Drake, so a similar actor is needed for this role.
Director: Joe Carnahan or Steven Speilberg
the reason I would choose either of these directors is because both know how to film action and suspense, while also forwarding character development, especially Steven Speilberg, since he is familiar with the treasure hunter genre thanks to Indiana Jones
So there is my Fancast, hope you liked it.