art...center over fireplace or center of wall  

Centered over the fireplace
would be my first inclination. Of course, without a photo of your particular interior, it's hard to visualize details that may influence the composition one way or another.
Let your eye be the final judge, though. Go ahead and hang it all three ways. The picture should be big enough to hide the extra holes!

That was my gut inclination...
That was my gut inclination also. It will probably look at a tad off either way since the fireplace is almost the same length as the wall but not centered in the wall. I'll try to post a photo of the wall in question.

It's often discouraged to hang
anything valuable or sensitive to environmental conditions over a fireplace that gets used. That means everybody just does it anyway, naturally.
A deep projecting mantle helps, and works on paper are typically glazed to help protect them, but you should still be aware that it can get incredibly dry and sometimes a bit sooty up there depending on design and frequency/duration of use.
And I'm really glad you're not putting a blasted TV up there. Whenever I see that, it just makes me want to tear my hair out and kick somebody.

It's not a working fireplace...
It's not a working fireplace so that isn't a problem. I rent from my sister and brother-in-law, and when they bought the place, it was going to cost mega-bucks to get the fireplaces into working order so they opted to make them just decorative instead. I probably wouldn't have used the fireplace anyway. I do have a fairly large mantle though.

usually...
Usually there is one way of hanging which will make the little differences in spacing less noticed. But as was mentioned above, you cant possibly know what will look best until you try...
My advice is: "don't even measure, just look". There are no rules when it comes to something like this. Go with your gut.
For isntance, over the years I have found that half the time, even "true level" does not even LOOK level! So I usually end up opting for whatever way does not draw attention to the inconsistencies.

There are tricks.
And there are some basic rules and common mistakes, but, you're right, EamesHead. Homes are intensely personal spaces and, in the end, the resident's preference trumps all.

.

yep... tktoo and Mark
..I agree with both of you. Indeed lots of tricks to this kind of problem...
My only point was that sometimes what LOOKS centered-- may not BE centered. (And the true center may not look right!)
You know what Michelangelo said when critics pointed out that his Virgin Mary was almost 7 feet tall in Pieta?
"The measuring stick is in the eye -- not in the hand".
LOL pretty radical notion but it makes total sense. He chose to go with visual "unity" over whatever the alternative was.
Bottom line: Whatever lets you enjoy the piece-- without the little measurement visuals becoming more "interesting" to your nervous system than the artwork!

Thanks, EH.
I always wondered why that nut would go at the Pieta with a hammer.

I never thought of that...
That's funny tktoo,
Maybe the guy was intimidated by tall women!

as long as
you do not hang your pictures too high. people tend to do that.it takes the balance and strength from the picture. saves craning your neck too...