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A lot of shows have continued to be great successes after the departure/death of a main character. Hell, hasn't ER lost most of its original main cast by now?
If we're talking comedy shows, Cheers survived fine without Coach and Diane. Only Fools and Horses survived and got even better after the death of Grandad. It all depends on the quality of the show. Talented writers will bring closure to the characters, introduce replacements in a natural way, and carry on doing what they do. Then, it comes down to the quality of the scripts.
If a JD/Carla-less season has better scripts than the last season, is funnier, then the show will still be enjoyable. If you ONLY watch Scrubs for JD or Carla, you're not getting the bigger picture.
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