I was playing in a Pathfinder "Skull and Shackles" campaign. The GM had put a ton of effort into designing distinctive speech patterns and personalities for all 17 members of our pirate crew, and he'd woven in his own ideas for a setting mythology where we weren't just questing for treasure, but trying to appease Besmara, the goddess of pirates. If we completed a quest in her name, we'd be named Free Captains, and would be metaphysically protected from law and order.
Well, our quest was to retrieve the jaw bone of a great whale that had once served Besmara. The jaw bone was kept by a sahuagin tribe, which meant we had to use waterbreathing and dive underwater.
We fought our way through their aquatic tunnels, and finally reached the throne room, where the leader of the tribe had the jawbone hanging behind his throne. A fight ensued - four PC pirates vs. the chieftain, his two bodyguards, and one wounded sahuagin who'd managed to flee ahead of us.
I said, "Someone kill the wounded one," thinking that it'd just take a single hit and then we wouldn't have to worry about being flanked. Well, that caused the rogue PC to split off from the rest of the party and attack the wounded one. Except the rogue only did 1d6 damage if he was fighting alone; if he were with the rest of the party sneak-attacking, he'd be doing 4d6 damage.
Then bad luck caused the rogue to spend 4 rounds missing that one damned injured sahuagin, while the rest of us got skewered and gnawed and thrashed. We ended with a TPK, which brought a really cool campaign to a crashing end.
I'm convinced that if I'd just ignored the wounded sahuagin, we would've dealt enough damage to the real threats to survive.