Test reconfirmation/renewal re-engagement methodology
I love it. If it's not yet considered industry standard practice, it's about time for that to change. Removing people who haven't clicked in years removes dead weight without killing your list. I regularly see it improve ROI, as you get the spamtraps and complainers out of the way, leaving only the people who actively want your mail and are most likely to respond. And you improve their ability to respond, by clearing out the bad addresses that cause spam filtering and blocks.
Read it, bookmark it, share it with your friends. This info should forever be ensconced in your personal "Email Marketing 101" handbook.