Many people will argue that the Battle of Gettysburg was the most significant of these because it broke the South's invasion of the North, which was the South's last good chance to win. I would argue, instead, that Antietam is more significant.
Antietam was significant for two reasons. First, it prevented an invasion of the North at a time when the South seemed to be winning the war. This made it hugely important on a strategic level. Second, it allowed Lincoln to issue the Emancipation Proclamation. He wanted to issue it, but he didn't want it to look like a move of desperation. The "win" at Antietam gave him a chance to issue the Proclamation. This changed the war, committing the North to the actual destruction of slavery.