Other things being equal, which they never are, a more powerful theme will provoke a more powerful performance. Yet some very dull books have been written about God, and some very fine ones about how to make a living and stay fairly honest.
For those who missed it earlier, I once came across Tibor Fischer talking about the problem of profundity in the arts. Or rather, the problem of profundity in certain artists. It's something you either have or you don't, and striving for profundity just makes you look belabored and silly.
And a big part of why you either have it or you don't, I think, is how you look at the things you're drawn to. As Chandler hinted, you can be drawn to very grand subjects but find that you have little to say about them, because you simply don't see anything that isn't already visible to innumerable others. On top of that, you haven't found a container for expressing what you see that is also compelling by itself.
I run into this problem a lot with fledgeling writers, who "just want to tell a good story". And while that by itself is fine, they always seem to believe the act of thinking too deeply about what they're doing will ruin it — an analogue of what I've called Cutting The Drum Open To See What Makes It Go Bang. But the other side of that is not engaging at all with what makes a story resonant in the first place — what compels people to go back and read it again, or even better, stand in line for when your next production comes out.
I'll have more to say about this later, as I have the final bit of Flight of the Vajra edits to put to bed this weekend.