And sure, this could be an email (all of the same principles would apply), but a letter makes things official in every sense. It also gives you a prop to take along to the face_to_face meeting with your boss, when you let him or her know that you're leaving.
A Professional Greeting. Your letter should be addressed to your boss. There's a good chance that this letter will merely end up in a file in HR, but it starts with your boss. Assuming this is someone with whom you work reasonably close with on a daily basis, it doesn't have to be super stiff and formal. Specific and professional is the right tone here.