Sure, it may sit in the depths of HR until the end of time, but you can be sure of two things: One, your former boss (and future reference) will read it and be impressed. And two, if you ever decide to come back to your company (hey, it happens), it's a very good thing that last thing on file is a great, professionally written resignation letter.
Prepare for It. This one is easy. All you have to do is smile and say "Thank you so much for your support. I've enjoyed my time here and I've learned a lot from you. Let me know what I can do to make the transition easier." Are you always going to get reaction number five? Probably not. But if you look for the signs, you can likely anticipate your boss' response, go into the conversation prepared, and come out stronger on the other side. Then, you can breathe a sign of relief and start looking forward to starting your new position.