David Moyes has cooled the pressure on himself with two consecutive wins but his side was embarrassed at the Etihad Stadium earlier in the season and faces a tough test Tuesday.
Victories against Olympiakos and West Ham, the former overturning a 2-0 aggregate deficit to secure United's progression in the Champions League, have served to dampen criticism of the Scot.
However, Moyes knows murmurings could intensify if the seventh-placed Red Devils again come up short at home against a bitter rival following its recent 3-0 home hammering by Liverpool.
While the Old Trafford faithful will be far from satisfied by another game in which its sole aim is to hinder a rival's Premier League title aspirations, a triumph would be a feather in the United boss's cap.
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For City, the game carries similar significance at the start of what will likely prove a season-defining run of fixtures. Currently six points behind leaders Chelsea with three games in hand, Manuel Pellegrini's men head to its neighbors brimming with confidence after a 5-0 drubbing of Fulham on Saturday.
But the visitors will be aware, too, that the derby precedes trips to Arsenal and Liverpool, which sandwich a tricky home game against Southampton.
Pellegrini will not be able to call on the services of key striker Sergio Aguero, who is another week away from fitness as he continues his rehabilitation from a hamstring injury, but Edin Dzeko looks set to be fit after being taken ill before the Fulham game and Stevan Jovetic should also be available, having returned from injury for the final eight minutes on Saturday.
"I think that this team doesn't depend just on one striker," Pellegrini remarked to reporters. "Maybe in the last week we had some problems with Aguero and Jovetic. Now Jovetic is coming back and I hope Aguero will be, next week, with the team. If they don't score there are other players that will do it."
Chief among the supporting cast is Yaya Toure, who boasts 16 Premier League goals this term following his hat trick against Fulham.
Moyes will, therefore, be pleased to have Rio Ferdinand available, having been forced to play Michael Carrick at center back against West Ham. Ferdinand was rested for that game but United will again be without Nemanja Vidic, who serves the second of his two-game ban.
At the other end, Moyes will surely deploy Juan Mata behind Wayne Rooney again as Robin van Persie continues to be sidelined.
City, boosted by the return from a ban of captain Vincent Kompany, heads to United following four successive Premier League clean sheets and are bidding for a third straight victory at Old Trafford in a row.