Ender is different: he knows about the war. He knows that he is being trained to fight in it. His fighting game gets ultimately wired up the the actual battlefield. The book is actually surprisingly ambivalent on whether Ender truely believes that this is still a simulation or something else. And when he is presented with the trigger (the MD device) he decides to press it. If I remember, he even kills half of his own fleet with that thing just because he does not see any other way to win.
I don't quite buy that Ender is complete innocence in this. He was trained to command these battles and knew what consequences his decisions have. Yet he makes the conscious decision to act as an intelligent being who is fundamentally able to decide otherwise if he wanted to. The alternative is set up to have terrible consequences, but it exists and Ender understands it. And the most damning aspect of all in my opinion is that Ender seems to suspect that it is not just a simulation anymore. Yet he continues as he always has.