The advice for cover letters in academia is the same as for cover letters everywhere: Always address them to a specific person, convince the reader that you're perfect for the job in question, and do it concisely. The greatest challenge for non-academic jobs is probably being concise; at least in academia we get two pages instead of a few paragraphs. The greatest challenge for academic jobs, at least for me, is customizing the letter for different jobs.
Sometimes that little extra is easy. With the right college, or at least an informative website, those little tweaks to put at the end or beginning of a sentence are easy: I am particularly intrigued by this program you offer, which demonstrates your commitment to undergraduate research. I believe my philosophy of teaching matches your department's statement endorsing a liberal arts education. Whether it's a special summer research program, unique courses offered in a special January term, or just some quirk about the college's history, there's something worth writing about.
Other times, however, that little extra effort turns into a lot of extra effort. The advertisement was cut-and-dried in its expectations. The college had no standout philosophy or curriculum. The department pages don't even supply much unique character, just the bare bones of research topics and course descriptions. I can search and search, and find nothing that inspires a single extra sentence about my qualifications and why I match their culture.
On the bright side, this customization works both ways. The hiring committee uses it to judge whether I'm really interested in their job; I also used it to judge whether I'm really interested in their job. The little statements I add are genuine, and make me feel excited about the prospect of being hired or even getting an interview with this particular college. That unique character will make me eager to get a position, even if it's asking me to specialize in my less-favored subfield. The fact that I couldn't find anything worth writing about says as much about whether I would want a job at that college as whether they would want to hire me.
I do not feel guilt or worry about my boilerplate applications. The cookie-cutter advertisement and website convinced me that there's enough possibility of a match to send my cookie-cutter application. Perhaps I'll get an interview anyway, and discover the wonders of a college that doesn't represent itself online as well as it should. Or perhaps I'll simply save my time and effort for colleges that do move me, and find the best match possible.
Or perhaps, if I'm still writing cover letters in the Spring, I'll become desperate enough to learn how to fake those custom sentences. Let's hope it doesn't come to that.