The cleric in D&D that I had the most fun with made it so that my Magic Missiles were still useful at level 15+. She had decided early on that reach-spell was a feat that was absolutely needed, and would routinely stock a few reached Harm spells. This meant that she had a 25' "Touch Attack" that ignored armor, and dex bonus. All you get is natural armor. If she successfully "touched" you, you now have 4 HP and a host of debuffs. Cue Magic Missile, and at that level I don't even have to roll because I am going to do between 10 and 20 points of damage, that cannot miss.

The first time we used it, she snuck attacked the boss in the middle of him monologuing, and I killed him in one move from each of us. DM started handing us three to four BBEG as boss fights after that.