For HarperCollins, yes, I knew an editor at one of their imprints because we were guest editors together last summer at BYU Writing for Young Readers. I asked her who in HR I should address my email to and then mentioned her name. At Tor, well, I'm not sure if it's because I mentioned my former boss's name (who is friends with the person I emailed, but I'd also met her at shows before too) or because I worked for one of their rivals and she knows the kind of quality stuff we put out. Then she sent me down to the MacMillan HR dept, where she'd already sent my resume to. I know editors at almost every major house because I've been going to editorial retreats, making sure to have lunches with editor bloggers when I went to conventions, and in general just trying to network with other editors as much as possible.
Now, this is harder outside of the children's book world--people in the adult industry, honestly, aren't as nice, I've found--but yes, you talk to every editor you meet at cons, you go to lunch and compare notes, you ask to pick their brains on work issues ("did you ever run into an author who....?" kind of stuff, no specifics of course), you ask them how they got started. A blog helps, too--I've met many editors in the virtual world who are now real-life friends.
And yes, from my experience, the only way you get an interview, even with my experience, is by knowing someone in the house. I applied for four or five other jobs and asked for several more interviews before I went to NYC (mentioning "I'll be in town next week," etc.) and never heard back from those houses, including one I was sure I'd hear from because I know one of their high-profile authors well.