ER. Happy Days where probably nobody noticed. Cheers that probably became a bigger success. Laverne and Shirley which lost Shirley. A Different World. Spin City. 8 Simple Rules. Sesame Street.
Fair enough, there have been some shows in the past that managed to find success, although I'd argue there are significant differences between those shows and TVD. 8 Simple Rules is probably also not a good example though, given how that show didn't last long after John Ritter's unfortunate death. Spin City also never recovered from Michael J. Fox leaving. Emergency Room is probably the best example, I had actually forgotten about how many actors left that show.
Then again, do we really need the show to go on much longer? The writers seem to have run out of ideas (and subsequently given up) seasons ago. Elena leaving the show would shake things up, but it wouldn't suddenly unmake all the crap from past seasons, nor would it suddenly automatically introduce good storylines.