The death of Buddy Holly is my vote. "The day the music died." Of course, that statement is predicated on an over-romanticized view of 50s rock-n-roll, which had more in common with country/western/gospel than anything else. I do not share that view, but the death of Holly was a big cultural event.
For me, the biggest tragedies (they're equal) in the whole of music history are the premature death of Wolfgang Amadeus Mozart and the death of Richard Wagner. It's clear that Mozart, from the non-Sussmayr sections of the Requiem, was beginning to head in a new direction that sort of prefigures Beethoven. In fact, in his 1991 Teldec recording of Sym. 39-41, Harnoncourt plays them as sort of prefiguring Beethoven in various ways. However, that aspect really comes to the front in the Requiem. It is clear that Mozart was beginning to head in the direction of Romanticism in some small way. He was still firmly grounded in the Classical, but there are hints of overtones of something new. Had he lived, there is no telling where he - and music - might have gone.
The death of Richard Wagner, at 70, was not unexpected - he was a bit old - but tragic for his loss. I recall reading that he had several new works, including a comic work, planned after Parsifal. His style advanced and progressed in such a way that another 5 or 10 years might have seen new advances and new waters charted. Since most musicians, until rather recently, have either been in response to or contradiction of Wagner, any longer of a life might see today's orchestral music scene radically different. Like Mozart, the tragedy of Wagner's death is a "what might have been" tragedy.