I think one the biggest losses (up their with Robin Williams) was James Gandolfini passing so soon. By all accounts he was a great guy. He personally gave cast-members $33,000 in order for the show to survive. Everyone on the show spoke very highly of him, I don't think there's ever been a negative word said.
https://www.businessinsider.in/enter...w/88420561.cms
He was a marvelous actor as well. Going back to his smaller character roles in Get Shorty, Crimson Tide, and even The Mexican. Then his best work (outside of Sopranos) was probably in Enough Said a few years before his death. He had a remarkable career. I'm almost certain we should have seen more Sopranos if he didn't die young.
Although I can't believe he was only 37 when the show premiered back in 1999. He seemed rather fit throughout the series, but he looked much older than 37.