If you, or she, has a GBA, or one of the DS's that can play GBA games, look for the "Eye of the Beholder" cartridge.

Yes, it's a party of 4, but it's a dungeon-crawler RPG, and very, VERY easy to play. Hell, I can finish it in a couple hours, without really trying.

There's a few RPGs that are suitable for beginners on the GBA. Would be a fairly easy entry into the genre.

On the PC, I'd go for a White Label (budget price Re-Release) copy of Diablo, or something similar - D2 was kinda more complicated, so probably not that good a choice for a first-timer.

I always found Diablo to be way harder than Diablo 2 thou, since D2 is horribly easy if you play with barbarian, paladin or assassin :P

My wife played the hell out of Oblivion, once she discovered Stealthing and it was over, she got scary good.... The only other game she played was Diablo and fable up to this point. Dungeon Siege 2 was anther fav of hers.

For a simplistic easy game i would highly suggest Oblivion since there is a on demand Difficulty slider.... or Fallout3 GoTY if shes more into shooters ^_^

Hack and Slash:

Torchlight (no co-op, there will be in Torchlight 2, though)
Titan Quest (really freaking awesome game, LAN co-op is great, so is expansion)

Traditonal RPG:
Gothic (very focused on story and choices, but has horrible controls)
Mass Effect (you can pause to use ally abilities or set them to auto, also you can hit Y to autolevel up any allies, massive Mass Effect wiki to help you out)
Fable: TLC is a good choice but very easy and even extended is awful short, Fable 2 is great with the dog
Fallout is actually really short and you can make her a bruiser that isn't too stupid and will do well
Arcanum has possibly one of the best RPG stories after Planescape: Torment, but is more accesible, I finished it with a very gimped character (made him that way on purpose) so you don't need to play perfectly to do well or have fun.

Also, a lot of folks really like Avernum, dated graphics, but has a long, long demo you can try (there's 6 installments): http://www.avernum.com/

EDIT: Stay away from Japanese RPGs, she may like them later but they can be super rough to start. Exceptions: Dragon Quest 8 (PS2) and Kingdom Hearts (PS2, if you consider this a RPG).

Contrary to the opinion of a few others in this thread, I'd actually consider Morrowind to be a good choice for an intro RPG. While the character creation can offer a fairly intimidating array of options, the fairly passive leveling system means that your wife wouldn't have to worry to much about the actual mechanics, but rather just play the game however she wanted and the character develops accordingly. Also, while the world is certainly massive and overwhelming at first, the setting and game design actually make this a good thing (as your character is basically dumped in a strange land they know nothing about). I personally think coming into it with little previous RPG experience actually helps add to the magic of the game (Morrowind was actually the first first-person RPG I played).

Also, Deus Ex would probably be a good pick. The mechanics are fairly straightforward while offering a very strong RPG experience and catering to a variety of playing styles. VTM: Bloodlines would also be a good choice for the same reasons as Deus Ex.

I forgot about Deus Ex, if you can find a copy, that is a strong choice (stay away from the second one, Invisible War, frustrating experience and ending). I like the Fable 2 better for passive leveling, if you use your gun you get mostly Agility experience orbs.

I would recommend Oblivion. After beating the main quest and exploring some of the world, I let my sister (who was sixteen at the time) create a character. She's probably the most casual of gamers, who before Oblivion had only played Rollercoaster Tycoon. She got instantly hooked and played for hours and hours. She eventually beat every single quest in the game, made a max-level mage, printed stuff out on the Oblivion wiki, and convinced my parents to get Shivering Isles for her. As someone who has played Morrowind and other RPGs, Oblivion got stale and boring very quickly, but for those new to the genre, it can be a fun and rewarding experience.

Jade empire (pre-Mass effect - and much better than ME)

Might I suggest reinstalling it and upping the difficulty to the last level? On normal yeah, the game is a piece of cake, from there on things turn interesting and there's a lot more strategy involved in fights.
If by any chance she finds it too easy/boring increase the difficulty level so that she'll feel challenged.

Also, take a look at these mods, as they add a lot to the game and balance it well.