#2 - Edge's cervical spinal stenosis catches up with him (2011)

Would you look at that - another World Champion getting injured during their reign! If you're noticing a trend here, good.
Anyway, brief history lesson - Edge suffered a serious neck injury back in 2003, which apparently plagued him for the remaining eight years of his career. After racking up a series of unrelated injuries over the years, he returned at the 2010 Royal Rumble and won it. He would remain in the main event for several months before finally winning back the World Heavyweight Championship in December of that year. He would hold onto the title through WrestleMania XXVII, where he successfully retained the title against that year's Rumble winner, Alberto Del Rio.
Did you know a top WWE Superstar just wrestled outside the company? More details HERE
This would be Edge's last match.
A week later, on April 11th, 2011, Edge revealed to the crowd that he had been wrestling through a considerable amount of pain over the last few months. Despite passing strength tests and making it through WrestleMania, WWE insisted that the Rated-R Superstar get a few more tests. He acquiesced, and tragically, the tests revealed that he would have to relinquish his title and retire from professional wrestling for good.
The diagnosis was cervical spinal stenosis, a bone disease that narrows the spinal canal in the neck. Assuredly the product of chronic degeneration stemming from his 2003 neck injury, Edge was very lucky he caught this when he did because he could have ended up paralyzed or even dead if he continued to wrestle.
Yet another case of a legendary career brought to a premature end.