Probably his involment in the Cardassian attack on Setlik 3
From a production point of view, O'brien was a down to earth every-man, a normal guy who had normal hobbies and a normal appearance.. He wasn't really exceptional in any way, save his engineering skills. An average joe who considered himself very lucky to have such a lovely wife, and a secure job. Hes a man most people can easily identify with.
As a result, hes also a man the crowd can easily sympathise or even empathise with. If sisko endures trama, well its sisko, hell muscle his way out. If Bashir suffers, he'll think his way out, being the augment that he is. But if O'Brien suffers, the audience suffers with him, feels sorry for him, and as a result, will care more about him, and that he's suffering. This in turn makes the audience hope more for the happy ending (rather than moe really cool wartime drama of ships blowing up and thousands dying), and makes the audience 'connect' with the fictional character on a somewhat more personal level.
In a word, while everyone else is larger than life, O'Brien is the average joe, and so is a natural target for the show's efforts to gain audience sympathy.
And I thought you were just going to say it's because he's an asshole....