My standard response when asked this question is
You Can Count on Me (2000). It was Kenneth Lonegran's directorial debut, and it's just a really touching movie. Definitely one the wife/girlfriend would enjoy as well.
I guess the best part of it is that the characters are just so "real". IMDB's plot outline is: "A single mother's life is thrown into turmoil after her struggling, rarely-seen younger brother returns to town.", but that really doesn't do it justice. Laura Linney snagged an Oscar nomination for playing the lead, and Mark Ruffalo deserved one as well. Rory Culkin and Matthew Broderick also have major roles.
I dunno what else to add. Just go see it - you won't be disappointed.