There are multitudinous ways in which it could end. (Of course there are, considering the lives that those two men lead.) Each is subtly different, though most are bloody and violent. Only very rarely is any sort of sickness a factor in the course of affairs, most of their endings being almost brutally fast. No time for heart-felt goodbyes (if they could find the words), shock sufficing to even suppress tears.
In one world, it ends before it ever begins. Sherlock overdoses at the age of twenty-seven, having concocted a speedball powerful enough to stop his heart before anyone could hope to find him. His body's already cold, limbs stiffening, when Mycroft forces in the door of his run-down flat only to be confronted by lifeless eyes. The funeral is a family affair – heartbroken parents, stoic brother, distant relations needing to be seen there instead of attending out of sentiment. Only one outsider, a police officer who hardly knew the young man and yet felt he should be there.
As for John Watson, the bullet that would have caught him in the shoulder instead embeds itself in his chest, wreaking a path of destruction so vast that there is no hope of stopping the bleeding. It's a long time before his sister hears the news from half the world away, so distant is she from him now.
However, that world is the exception to the rule. More often than not, Sherlock is the one with his life ended in a haze of gunfire, bullets piercing his neck or forehead or chest, or that one time where it somehow manages to destroy the femoral artery in his left leg. Usually, those are the worlds where he and John were destined to only ever remain as friends, and sometimes it isn't even the initial gunshot that kills him, but the aftermath. In one world, he dies on the floor of 221B after bursting his stitches in his escape from hospital. In another world, one where he and John do actually get together, it's a hospital-acquired compounded by post-traumatic pneumonia which ushers him into the next life.
There is little logic as to why it is usually Sherlock who dies in the moment of traditional glory, but it may be surmised that John is better able to deal with it than Sherlock would be. In fact, some consider it more than likely that Sherlock would follow John all too quickly if their roles were reversed. (There's a basis in reality for that – time and again in different worlds where John is the first to go, Sherlock seems to hardly cope. Be it drugs or tracking down serial killers, or those ones where he retreats into his mind, a well of despair, oftentimes he slips away from life faster than anyone can properly grasp.)
There is one world where they die together, a bomb in Baker Street ripping their world apart without warning. Mrs Hudson is – luckily – away at the time, and after he gets the news, Mycroft takes it upon himself to arrange alternative accommodation for her. Though everyone finds it difficult to comprehend that John and Sherlock are gone, in a way they are oddly relieved that at least it is together, and not one left without the other.
(Sherlock was the first to die here too, almost instantly, neck snapped as the building collapsed around him. John was beside him, crushed beneath the rubble, but blissfully unconscious for the handful of minutes that he lived in a Sherlock-less world.)
Though it usually ends in death – be it the incident at Bart's going badly awry, or something in the intervening years, or the affair in Magnussen's office or a variety of other ways – occasionally, just occasionally, does it end otherwise. Time and two years separated serving to divide those two men, forcing them to grow apart no matter how much they attempt to deny it, or fight to hold on. No matter how well they try to hide the pain that this eventuality inevitably brings, it is always there, always lingering in the subconscious, the idea of all of the other things that could have happened, the way that things could have ended for them if they'd only fought harder. (In truth, there is no way for them to fight harder in these worlds, but the longing to still remains, haunting each no matter what other twists their separate lives take.)
No matter how it ends, it always hurts, one way or the other. The might have been always consumes their thoughts, be it separation through death or time, regardless of whether they get together in a romantic way or not. Too much pain, too much heartache, too much silence on one part or another. There is no other way that it could end for them, except for one. (Sussex, cottage and bees, too old men together with a lifetime of stories tell, a shared history, taking comfort in each other even at the end of all things for them.) And that one world is infinitely more precious than any of the others.