I felt it was handled very appropriately in Madden '92
http://www.youtube.com/watch?v=_138p6uzhUk

The side effect here is that a new strategy will appear where one intentionally tries to injure the other team because they know they can't come back in.  This isn't real life where there might be a resistance to seriously injuring other human beings.  Who cares about videogame characters?  I'll mow down 100 videogame characters without batting an eye.  So instead of emphasizing the true injuries that can occur in football, it becomes part of the gameplay.  You can cause injury which can give you an advantage and there is no real world guilt or repercussions.  So it becomes a strategy and more emphasis is put on hurting others.

It's like if you make an FPS that shows the real effects of getting shot.  Well that just plays up for gore freaks.  Murder simulation becomes part of the gameplay.  Ironically if this didn't emphasize the injuries it would just be about football strategy.  Without injuries as part of the gameplay the goal becomes entirely to sack the quarterback because there is no reason to "kill" the quarterback.

Yeah, I agree with Ian.

They already kind of do this for their FIFA games. If it were real soccer, I would feel bad about flying in with a slide-kick, injuring a player. But when it happens in the game, I cheer. And thanks to the usually lenient calls as long as you slide from in front of the players, I do it way more often then I would in a real game.

Injuring players became a strategy, albeit a small strategy, but one none-the-less.