Superman
Explanation
The Joke
Superman approaches an economist to ask how he can best use his incredible powers to help humanity. Instead of suggesting he fight crime or stop natural disasters, the economist explains that Superman's powers would be far more valuable if applied to industrial production or infrastructure — for example, by using his super-strength for cheap heavy lifting, or his heat vision for efficient manufacturing.
The punchline is that Superman would save vastly more lives through economic productivity than by punching villains, but this answer is deeply unsatisfying from a narrative standpoint.
The Humor
The comic is a classic SMBC move: applying rigorous rational/economic thinking to a scenario that is normally governed by narrative logic. Superheroes fight crime because it's dramatic, not because it's the optimal use of their abilities. An economist would correctly point out that the opportunity cost of Superman stopping bank robberies is enormous when he could be, say, launching satellites into orbit for free.
This touches on the effective altruism concept of "comparative advantage" — even Superman should do the thing where his marginal contribution is greatest, which probably isn't fistfights.
Why It Resonates
This comic has become a touchstone in discussions about effective altruism and rational philanthropy. It's frequently cited in EA communities as a humorous illustration of how intuitive notions of "doing good" often conflict with what would actually maximize positive impact.