The genius of e=mc2 is not in its application to nuclear physics, it is in the conceptual breakthrough it provided in our understanding of our universe. From there we have entered a modern world totally unlike the old one. A world in which more can be imagined and new frontiers can be opened.
The genius of e=mc2 put Einstein in the company of Newton. The story of the apple falling on Newton's head leading to his understanding of gravity hides the genius of his epiphany just as covertly as a mushroom cloud hide's Einstein's. Newton's genius was realizing that the apple pulled on the earth with equal force as the earth pulling on the apple. This is an amazing insight. Put this idea along side his laws of motion and you have the foundation of all of our engineering from bridges to tall building to space travel.
Einstein realized that matter and energy were the same and that the speed limit of light provides the connection. This amazing insight provides the secret to the stars, but it is also the secret to our modern understanding of the world around us. His insight allows us to consider the origin of the universe, the existence of black holes, the possibilities of time travel, and much much, more.
E=mc2 ushered in the golden age of science fiction as well as spawning a renaissance of science. History may show that the period of time when Einstein worked surpassed the enlightenment in significance. If this legacy is true, it is because of the imagination unleashed by Einstein's ideas.
Check out NOVA's site about Einstein and his famous equation: