it's done in indiana jones: and the last Crusade. They have the drinking from the grail and if you drink from the wrong one you melt (sort of).

While it can stand on its own, I think it would be better to not do something that heavily inspired uncharted in the first place. Particularly when there's other things, that haven't been done nearly as much as the holy grail. 

canada. lewis and clark.

Atlantis, South Asia, East Asia, Russia

Retrace the footsteps of Marco Polo and end up in rural China.

You know what I would like to see? Something kind of like The African Queen. A journey into the depths of Africa with all the violence and brutality on either side.

Well it's obvious.

Exactly that. Much like how Uncharted started out before becoming a gritty shooter http://www.nowgamer.com/news/1063301/naughty_dog_gritty_xbox_shooters_shaped_uncharted.html

To the Moon.

I don't have any specific preference really - I just want it to feel fresh and fun. I'd say Caribbean, but the geography, climate, etc. are similar to the settings in UC1 and UC GA, so it may not 'feel' different. I'm not too much a fan of the setting in cities, at least for long periods, so I hope the next game balances the city space and the outdoor environment.

I like the flashbacks, so I hope that's something they do again.

So far, we've had the jungles of somewhere in Indonesia, the tundra of Tibet and the deserts of the Middle East (though to be honest he didn't spend very much time at all in the latter). Perhaps some light English woodland for the Holy Grail this time? Or perhaps something in Japan: I'm sure they can find a legendary Japanese artifact.