I'm going to disagree on Strangers in Paradise. I like Strangers of Paradise, and I own the whole series in omnibus, but I wouldn't recommend it to most people. There's a lot to like about it, but at the end of the day, it was the guy's first comic, and it really shows. The storytelling oscillates wildly in tone and quality, and whole plot lines disappear without warning, never to be seen again. (What ever happened with that bomber?) When it's good, it's great, but when it's not great, it's really uneven. It's a great comic if you like to watch as a comics artist/writer figures out how to make comics - which is why I was delighted to finally pick up the Zot! omnibus, and why I have a soft spot for Megatokyo. But for somebody who doesn't already like comics and doesn't have an existing interest in the underlying craft, it's not a good choice.
I'm going to have to say that the best comic for people who don't read comics is still Scott McCloud's Understanding Comics. I loaned it to my 7th grade English teacher, who was not a comics person; he kept it for two months, returned it, and asked if I had any other comics worth reading. You can't argue with results.