My one pain point is that people who are indecisive about trading make me want to gouge my eyes out with a spoon, since play slows... to... a... crawl.
For me Settlers is at the sweet spot for board games where "casual" and "serious" intersect. You can play it with non-gamers, games last an hour and a half (Monopoly never finishes that quickly!), and pretty much everyone enjoys it on their first play and understands it on their second. On the other hand, board game geeks happily play it and the game rewards skill. It scales well with player experience.
The rules are no more complicated, either. Just make sure you're getting them right so that balance isn't thrown off, which can make the game not fun. Play a few games online at http://games.asobrain.com/ where the program will teach you the correct rules.
This is why I like skill-based yet luck-dependent games like Scrabble or Trivial Pursuit. Even if you're 150 points behind in Scrabble, there's always the chance you're going to get two great racks in a row. And even if you're six pie-slices behind in Trivial Pursuit there's always the chance that you'll get a long run of questions you happen to know the answers to.
The diplomacy aspects of this simple card game don't become apparent until you start playing.
As for the humor on the cards, you'll have seen it all in two plays (especially since the game drags on for a while). This explains the healthy market for expansion sets.
I'd also recommend Tigris and Euphrates, Ra, Puerto Rico, and a host of other "German-style" games.