Here are a few examples of mysteries (I just came up with them now):
A. A woman finds out that a lost ancient city still exists.
B. A man finds out that her death wife is actually alive.
C. The TV of a guy keeps turning on at night even though it's not connected.
Would readers care about all of them? If so, what would make them care more about, say, A than B, or B than C?
I think what makes anything matter to readers is:
All people have a natural curiosity.
The mystery genre usually preys on that curiosity, giving people a hypothesis and asking them one or several questions based on that hypothesis. This is the 'mystery'.
Then they try to solve the said mystery in their minds and this involves them in the story a great deal. Because it makes the story personal for them. They want to see if they got it right.
If they did, and if it was not too easy (because then it's boring), then they have a sense of satisfaction, feeling smart about it.
If they don't (and they usually don't because most stories withhold information from the reader or, better, cover it very good as to not raise a hint) then they are left in a sense of awe at the right answer.
So you can't go wrong with the mystery genre.
However, when creating a mystery, you can go wrong with writing it. Make it too easy and the story can become cliche or uninteresting. If I can spot the real killer from the beginning, I'll dismiss it as a dumb story. Making it too hard, usually doesn't go wrong, but in my experience you can never make it hard enough without outright withholding information from the reader (which is a bad idea, since they'll feel cheated) or employing techniques like the 'Deus ex machina', that readers usually hate.
You have to find a balance, and have the character in charge of solving the mystery keep pace with the reader's own judgements.
I must add the "solving the mystery in one's mind" must not necessarily be a conscious act (you don't have to make notes of events and characters and deliberately try to solve it). It often happens subconsciously and it's the reason we gain interest in the mystery. Your brain is subconsciously trying to find an answer, given the hypothesis, and it is this very thing that makes you react with interest toward the said plot.
Now, as for what mystery pique's a reader's interest, well, it depends on the reader.
From the three choices you enumerated, I'd definitely go with C.
A doesn't interest me because I don't have a fascination with lost cities and the plot itself does not raise interesting questions for me (question's like what might we found there). Also if you plan to make a plot out of it, I advise you to build up the legend of the lost city as to make it interesting to the reader. Make them wonder about it. Make them want to go there to explore. And only then reveal it's continued existence. If you don't build it beforehand, the reveal will fall flat and won't pique the reader's interest.
Same with B. Make the dead wife known to us. Either through flashbacks or her being a character before hand. Have her disappearance or death be somewhat of a mystery for us. If readers don't know who she is, they won't care that she's still alive. Make most of the reveal to hook the readers further with your story.
With C, the mystery index is rather high. First it's something we can all relate to (at least we who have a TV). Then it has a dose of unexplained, pointing toward supernatural phenomena, which has always piqued the human mind's interest, because we seek to make sense of the unknown.
The first two are circumstantial mysteries, which depend on further elaborating the mystery around them to make them good. The third is a mystery in itself.
That absolutely depends on your story. If it's important for the story, readers will be curious. But then, don't disappoint them ;-)
