While i personally prefer epic-scale Ameritrash games, I'm always on the lookout for a game to play with my parents, brothers, and wife. They've been hooked on Settlers of Catan for a long time, and we recently started playing Carcassonne when we get together. But I definitely get the sense that they enjoy the more frequent interaction of a game with a trade element, so that you're not just waiting for your turn to come back around. From FFG's product description page, it looks like Constantinopolis is definitely one to keep my eye on...
I am in the same boat as you. My Wife loves Settlers and has been on me to get a new family game. We have tried the commonly recommended games, like carcass and agricola, but, those games are snore fests. Besides the Wife, I have two teenagers that like games, but they can't be A) To nerdy - so nothing amazing like Runewars B) Too simple, so no Clue ish games C) Fun, so Carcassone is right flat out D) It has to meet the discerning judgement of teenagers. Which is tricky. I downloaded the rules and they seem simply enough. Just hope to get a intro game in at the LGS sometime.
Tried a couple of other games, but just can't get that wow factor from the Wife.