Kevin De Bruyne and Riyad Mahrez both scored twice as City condemned their rivals to a humbling 4-1 loss on Sunday.
"I think the worst thing you could say about United is they did give up," Keane told Sky Sports.Â
"For a player in a derby, or any game, to give up, it's unforgivable really.
"The beauty of top-level sport is there is no hiding place. We saw all United's shortcomings today.
"There's ways to lose football matches, we've all lost football matches, but the way United lost today, they stopped running, they gave up. There's players out there not running back.
"That's what I don't understand. The manager will be criticised, and the tactics, but players not running back when they are playing for Man United is unacceptable.
"They threw the towel in, which is shameful.
"I forgive mistakes, but you've got to run back. There's five or six players who should never play for Man United.
"A couple of lads in midfield, (Aaron) Wan-Bissaka, Fred, (Marcus) Rashford came on. I could go on. And City weren't even at their best. They didn't have to be.
"They gave up, Shame on them!"
Former United and England full-back Gary Neville was equally scathing in his assessment of their performance.
Sky Sports pundit Neville said: "Manchester United ended that game like an absolute shower. They were a disgrace.
"They came up against a proper team and they've been given a proper doing."
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