Act III is significant because by the end of the act all is how it should be. Lysander and Hermia will be together again, Demetrius will love Helena, and Oberon has released Titania from the spell and they have resolved their discord. What is interesting is that Oberon interference and Puck's mistake have made the outcome better than it could have otherwise been - particularly with Demetrius no longer loving Hermia but returning his affection to Helena.

I personally think the line "The course of true love never did run smooth" by Lysander in Act I, Scene 1 is significant because all of the couples in the play had to overcome obstacles in their relationships to be together.