No Religion
Religion and its extreme impact on diplomacy is no longer part of the game. In previous CIV-Games one could make enemies to friends, if chosen your religion wisely. Moreover the spreading of a religion with missionary priests belongs to the past.This indeed has a big influence on city planning and the game-progress itself. Because all buildings one could build fitting to a religion - temples or monastery for example - approximately won't be there anymore.
At first glance this is surprising, as it was religion which promoted civilizations in real history for the last millennia. However, regarding to Lead Designer John Shafer, in past Civ-games the element religion mainly had an influence on diplomatic activities, because it split nations into several "blocks". Obviously this effect didn't fit into the new emphasis, the forming of alliances.