For me, it would mainly be ,Graham Chapman one of the iconic Pythons, as well as Nathan Fillion or Joss Whedon. If either (or both, god forbid!) died, there would be no more hope for Firefly, there would be no more Castle if Fillion died, and likely no more good ensemble films or series if Joss died. He does those spectacularly.
And as for Graham... Well, he's one of the surviving Pythons, and really, hes a living legend in British Comedy, or at the very least should be. I would most definitely mourn his death.
Of course, honorable mentions go to Sean Connery, Morgan Freeman, Bruce Willis, and last but certainly not least, Tim Schafer.