Well based on trends, we can make several assumptions.
1. Joel has a deep seated mistrust or reluctance toward institutions...of any sort really. Fireflies, hospitals, the police force, military, schools. In fact, most of the conflicts in the game revolve around institutions. Government buildings, schools, hospitals, labs, etc. He lost his daughter to military, he lost his companion to military. And each time, they weren't due to being bad guys, they were caught in hard places. Ie, daughter shot despite not being infected, companion shot despite trying to save the world.
While it's not really evidence, we could theoretically make inferences. However, we also never really see this mistrust appear until his daughter dies. He's even incredulous that they aren't allowed to pass.
2. Joel is plagued by a failure to protect his loved ones. Each person he loses dies under his direct supervision. It is ellie who bucks this trend by surviving herself and protecting joel. Ellie has surpassed joel. We could make the inference that joel somehow let his wife die or was not able to protect her.
3. I think it's pretty obvious his wife died, which is clear by the lack of any mention of her during the story or with Sarah during the outbreak.
4. We know joel has a revolver, while some might point out that owning a revolver is simply something people do, it's also a move toward protection.

There's a lot that one could glean from the central themes but I think the most important factors are these:
Inability to protect loved ones
Bad feelings toward institutions
Over preparedness resulting from inexperience
Self loathing

I'd say a couple possibilities are:
Drunk driving accident with joel at the wheel
Sickness complication/hospital related death (miscarriage)

Then there's the whole theme of the game, which is:
Survivalists struggling in post-apoc society caused by parasitic natural phenomenon.
Other central themes are children, family, betrayal (government betrayal, firefly betrayal, betrayal of the gay dude by his lover, betrayal of species against itself)

You could kind of boil it all down to something natural/human nature/biology stops functioning normally and results in destruction.

Having not played the game in over a year, I'd honestly saymy best guess would be something involving a betrayal of self through lack of control, becoming a monster.

I'd imagine a fight about something, maybe their future, possibly while drunk, causing her to leave and somehow die maybe by car accident or suicide.

Oh I just thought of another trope: direct conflict opposition:
Police are supposed to protect but kill Sarah
Humans are supposed to die, not come back to life
Joel learns on the streets not in school
Firefly supposed to cure not kill
Joel loves but shows it through anger
Maybe he needed her and she left
Also sarcasm is truth hidden in a lie

Another interesting question is about the watch. Why did his daughter get him a watch? And why did joel make a joke saying it was busted?

Sorry for the rambling but I'm on my phone and everyone knows how difficult the process of editing on vgc via phone ia.

And wow at divinepaladin you sir are a bona-fide hater. Similar tropes can be found in the movies district 9 and children of men.
It's a highly influenced plot by some much greater art pieces, but that doesn't mean it's just an average, superficial, trite story.

Would you say the remake of romeo and Juliet with Leo was an "average plot"?

The point is, yes it's stolen or influenced heavily, that doesn't mean it's bad.

I assume she left Joel for another man and started a new family.

They eventually met Ish, and she was the bitch who left a door open and got almost everyone killed.

That's not the point. Not ONE SINGLE person has wondered what happened to the mother. This is sign of the times unfortunately.

I'm not sure that second part is true, but it is definitely possible that she left Joel.

They were probably too busy thinking about Joel and Ellie's relationship?

Why would ND ask about the mother? It's a sign of the times that not a single person asked about the mother. That's how disposeable parenthood is nowadays.

Or it's just a sign that ND made her completely irrelevant to the story, and to a lesser degree, made Sarah irrelevant as well. She only existed to build Joel's character background. The story was about Joel and Ellie.

Also, it's impossible for you to say absolutely zero people have ever wondered or talked about the mother.

http://www.gamefaqs.com/boards/652686-the-last-of-us/66507912 Here are people talking about the mother.

http://community.us.playstation.com/t5/The-Last-of-Us-General/Spoiler-Tess-was-Sarah-s-mom-Joel-s-daughter/td-p/41212325 More people speculating about the mother.

I'm sure I could find a lot more if I bothered. People have pondered the identity of the mother and why she and Joel split. It's not a big deal in LoU discussions simply because it was irrelevant in the story.

Here's a good question, is Joel ever wearing a ring?

Just discovered that the pic in Sarah's room are Sarah's friends.

I'm going to go ahead and say died during childbirth, that would fit in with the mistrust of institutions, and the "parasitic organism consuming the host" themes.