The first famous failure which comes to my mind in replacing the irreplaceable belongs to the Dead Kennedys. One of the greatest punk bands ever, the Dead Kennedys were Northern California's gift to the underground, at least until they decided to reform without original singer Jello Biafra in 2001. The iconic Biafra's voice helped make the Dead Kennedys' signature sound unmistakable, and his particular way of phrasing chorus and verse alike is unlike any other in music, let alone punk rock.
Now, though, the Dead Kennedys are a joke band whose instrumental brilliance is cheapened to the point of repugnance by possibly one of the worst choices in rock history as replacement vocalist. New singer, Ron "Skip" Greer has no presence and, sadly, attempts to mimic Biafra more often than not. At least he doesn't try to emulate Biafra's classic pantomime stage presence. If you're looking for something at least close to the power of the Dead Kennedys circa 1983, then check out Jello Biafra and the Guantanamo Bay School of Medicine next time they come through your town. You won't be disappointed, but if you are longtime DK fan and you go to a Dead Kennedys show, you just might puke.
Is there a more famous or notorious example of replacing the irreplaceable than Van Halen? When they first announced Sammy Hagar as a replacement for David Lee Roth in 1985 and Van Halen became Van Hagar, I couldn't believe the utter bullshit they put out. While I never really got into Van Halen after their first record, there was no denying their power as quartet led by Roth, and it has to be said: Their eponymous debut is a great, great record.
There was something a tad dangerous (although now it seems more ironic than anything else) about Diamond Dave, but all of that was out the window when they brought in Sammy Hagar. The success was there and fans eventually accepted Hagar to the point of millions of records sold and packed concerts everywhere, but there was always something missing. Even though they don't play very often anymore, Roth is back these days, even if the band's relevance is not.
The Who keeps trudging on even though its original rhythm section, led by virtuosos John Entwistle (bass) and Keith Moon (drums), is now deceased. Moon died back in 1978, and Kenney Jones of the Small Faces/Faces got the unenviable task of being his first replacement. Needless to say, the drumming on Who recordings post-Moon were never inspiring, although current drummer Zac Starkey more than holds his own. When Entwistle died in 2002, many Who fans wondered how they would replace him and while Pino Palladino is a capable bass player, he is not even close to being a suitable replacement for the The Ox (Entwistle).
The Who at their best: