The successfully Kickstarter-funded Expeditions: Conquistador will be getting a 28 February release. This tactical RPG (with added dabs of resource management and choose your own adventure) raised $77,000 USD back in September and is now approaching completion.
In it, you can opt to follow history and be a total Imperialist dick in South America and Mexico, or you can try to follow the path of peace and navigate your way through the world with diplomacy. Either way, your unfamiliar germs are probably going to make the local people pretty ill.
For a decent idea of how the game plays, have a watch of this 20 minute+ demonstration video by Danish developers Logic Artists.