Ralf Rangnick’s side failed to register a single shot in the second half, entering the break still in the game at 2-1 after Kevin De Bruyne’s goals either side of an equalizer by Jadon Sancho.
Riyad Mahrez netted a second-half brace, his first strike effectively ending any competitiveness in the game, as United’s first four ambitions took another hit.
And former United captain Keane was furious at what he saw from the visitors, criticizing the lack of commitment from a number of players.
“We just saw a reflection of where the team is and where the club is,” Keane said.
“Whatever is going on in the dressing room and we hear about issues with the arrival of the new manager, but ultimately your own pride has to come into play at some point.
“I will forgive mistakes, but you have to step back. There are players, and I write five or six of them, who should never play for Man United again. It’s shameful, just shameful that you can’t go back and put your body on the line.
“The submarines came, you thought they would have an impact, but they weren’t ready to run everywhere. Wan-Bissaka, Fred, Maguire, Rashford then came on. I could go on.
“I allowed four goals and City didn’t need to be at their best. I thought City still had a few gears to go.
“They gave up and shame on them.”
United hadn’t lost at the Etihad since 2018 before the game, but things quickly fell apart in the second half as problems under Ralf Rangnick continued.
Keane insisted that the focus should be on the players and their work rate, rather than a tactical approach.
He said: “The beauty of high performance sport is that there is no hiding place. We saw all of United’s shortcomings today.
“There are ways to lose football matches. The way United lost it today – they stopped running, they gave up. Players not running backwards, that’s what I don’t understand.
“The manager and the tactics will be questioned, but the players are not coming back while they are playing for Manchester United. It is really unacceptable. They have thrown in the towel which is shameful.