I only saw after writing this that an excellent comment suggested the same kind of disaster. I've added some comments to address the OP's concerns about plausibility.
A seminal event in a story I'm working on requires a tragedy that will kill hundreds (or maybe even low thousands) of innocent bystanders. [...] My first inclination is for a skyscraper to topple...
In case you're willing to consider other kinds of events:
Supernatural weather conditions, power disruptions, or plant growth—or even just a super strong punch—could break a large, poorly maintained dam, like the one that holds back Atlanta's Reservoir No. 1, or the Willett Pond Dam near a suburb of Boston. You can refer to the dam's emergency action plan for guidance on what might happen next. In the case of Reservoir No. 1, the AP reports that "If the dam were to catastrophically fail, the water could inundate more than 1,000 homes, dozens of businesses, a railroad and a portion of Interstate 75." In the case of Willett Pond, they report that "If the dam were to give way, it could send hundreds of millions of gallons of water into the heart of the city of nearly 30,000 people." This is really bad—and if the setting of your story has even more development in the path of the flood wave, the potential for injury will be even worse. 87
City planners should try to prevent risky development like this, but they'll have little power to stop unscrupulous builders with city councilors in their pockets, or desperate people with nowhere safer to sleep.
Could the combatants plausibly cause this kind of failure? If the dam is already in danger of breaking, I'd imagine that a strong impact could set off a failure cascade. An especially dangerous situation, mentioned in the AP article, is when the water level behind the dam is too high, and problems with the dam's spillways make it impossible to let water out fast enough. This can lead to—and, unfortunately, has led to—spontaneous failure. The AP article also mentions other conditions—"leaks that can indicate a dam is failing internally; unrepaired erosion from past instances of overtopping; holes from burrowing animals; [and] tree growth that can destabilize earthen dams"—which I'd imagine could put a dam in danger of breaking even at nominally safe water levels.
The combatants' powers could contribute to a catastrophic dam failure in very subtle ways. For example, someone with power over weather might attract heavy rain around them while they fight. This wouldn't normally put anyone in danger, even during an hours-long fight near a reservoir; after all, the dam has spillways to handle flooding! If the spillways aren't working because of poor maintenance—or because the other combatant's electricity-disrupting powers have put the control systems out of commission—it might not be apparent until it's too late. As another example, a fight involving someone with power over plants could agitate nearby trees, causing them to shake and writhe. Tree growth, as the quote above says, can destabilize earthen dams—and some of the dams the AP read about were "so overgrown with vegetation that they couldn’t be fully inspected." 87