1. One word: Maus.

It's a story of a man who, over the course of two volumes, chronicles his father's story about surviving the Holocaust. It's funny and sad as all hell, as you can imagine, but it's an amazing narrative and a really touching look at the relationship between father and son. Everyone is also rendered as animals, which sounds laboured, but it works beautifully.

It IS the most obvious answer in the world, but I can't say I've ever regretted giving it.

2. This I personally consider fairly strong fantasy, but another one word: HELLBOY. Fanta-bulous. Lots of folklore, wrapped up in gorgeous, graphic art with a gothic twist. It's not so much classic high fantasy -- think Tolkien -- as this more ancient strain of story. Mike Mignola draws upon a lot of European mythologies to populate and fill out his stories. He hints at a deeply old, rich world.

The first volumes tend to be short stories, so they're easy to digest, and they throw you right in, so there's little mythology to absorb beforehand; you learn it all along the way.

The characters are all intelligently written, and Mignola's crowning glory, Hellboy, is dry and engaging. BRPD, the sister series, is just as good, and possibly, better in some ways.

Fun Home by Alison Bechdel is amazing.

So many wonderful possibilities!

Maybe no surprises here, but I'm thinking Alison Bechdel's Fun Home, Jessica Abel's La Perdida, David B's Epileptic, Daniel Clowes' Ice Haven, Marjane Satrapi's Persepolis, War's End by Joe Sacco, The Rabbi's Cat by Joann Sfar, Mister O by Lewis Trondheim, Abandon the Old in Tokyo by Yoshihiro Tatsumi, and Locas by Jaime Hernandez. I don't think there's a single title there that isn't truly excellent in its way, or that would be at all off-putting to a reader new to GNs.

Another way to go would be some excellent samplers of various styles, such as Ivan Brunetti's Anthology of Graphic Fiction, Cartoons and True Stories, and volume two, or the Best American Comics series.

I really got into Sandman when I was first looking for graphic novels for personal reading. Cliche perhaps, but it worked for me.

Dash Shaw's Bottomless Belly Button is also good, if a monochrome novel is something she'd consider reading.

I don't know if the Flight books count because they're anthologies of shorter stories (some continue from volume to volume, some are one-offs). Nearly all the stories intersect with the idea of flight in some way, and the artwork is achingly beautiful. I believe there are 7 volumes out now. Check it out!

http://seattle.bibliocommons.com/item/show/2689369030_flight

How about Stitches by David Small?

I second everything LMNOP said. Hellblazer and Miracle Man were a couple more that sucked me in. Y, the Last Man is good too.
But frankly, I'd start with Sandman. There's just no way to go wrong with that title - especially for someone who is well-read.

Blankets by Craig Thompson.

I'd say Sandman or Fables if she's into the Sci-Fi/Fantasy stuff and doesn't want something too testosterone filled.

However, every girl I've introduced to Preacher or Transmetropolitan, even the ones who haven't read a comic in their lives, were instantly hooked, despite the more testosterone-y feel to them. Plus, they all ended up with crushes on Spider Jerusalem. So the "for an adult woman" portion of this equation doesn't need to have anything to do with it.

Well, I agree with everyone here, honestly. You probably won't go wrong with any of these suggestions. I'm coming in a bit late to this party, but I can't resist evangelicizing comix, especially if there is the posibility of another adult female fan on the line. (I love comic-loving ladies!) Here's some other titles to consider:

Polly and the Pirates, or the Courtney Crumin series by Ted Naifeh. Anything by Ted Naifeh really. Great stories, kick-ass girl heroines and awesomely accessible art.

Ghost World. If your wife was a teenager in the '90s, she might really identify with this book. Super snarky and funny angsty.

The various biographies and Victorian murder stories by Rick Geary. Fun for the history buff and people fascinated by the macabre. Lizzie Borden murders, J. Edgar Hoover, Lindbergh kidnapping...

Also for the history buffs; 300 by Frank Miller. Ignore the movie, it was "eh," comparatively.

Locke & Key is my current favorite. Good modern gothic fairy tale stuff by Stephen King's son, Joe Hill. Really pretty artwork and colors, too.

Astro City by Kurt Busiek. Really good stories about the human side of superhuman. A nice, intelligent take on the typical superhero genre.

Strangers in Paradise. Pure soap opera, done at its finest. Lots of drama, love triangles and cliff hangers.

Cairo, by G. Willow Wilson. She's drawn some flak for her novel about her Muslim conversion (which I haven't read), but I think her comics are great. Also, she's local.

Finally, Usagi Yojimbo by Stan Sakai. Sort of a cross between Disney and Akira Kurosawa. Cute artwork with in-depth stories that pull from the history and folklore of feudal Japan.

I see your "Blankets" by Craig Thompson, and raise you one "Goodbye Chunky Rice"- also by Craig Thompson. It's sweet, and smart and accessible. I consider this the ideal gateway graphic novel.

I know these are pretty mainstream and pedestrian, but V for Vendetta and Watchmen might be good first steps--they're the only graphic novels I (an adult woman who loves fantasy and doesn't mind scifi) have read, and I found them pretty easy to get into. Also, I hear great great things about Sandman from virtually everyone.

God Loves, Man Kills by Chris Claremont

or The Death of Captain Marvel by Steve Englehart?