To be honest, I dont know. I'm actually not an American. :)
But If i had to pick one major event...it would be making George Washington the president.
To explane.
George Washington's presidentsy in a way made America, in some aspects, what it is today.
Now imagine if he was not made a president but chose to be a dictator. I know its funny and my nest statement is going to be even funnier.
Assassins Creed 3: The rule of King George did a decadent job in imagining and explaning this. I recommend reading its plot, I think you would find it interesting. Its full of what ifs and alternative history events.
Sorry for not giving my version but its a bit hard for me to imagine something like that.