Ole Gunnar Solskjaer's in-form team have a chance to severely dent Liverpool's chances on Sunday when they host Jurgen Klopp's side in a fixture that has weighty historical importance to go with its significance in the title race.
The match is effectively Liverpool's game in hand, with City, level on points at the top of the table after playing a game extra, facing Chelsea in the League Cup final on the same day.
But they face a rejuvenated United under interim boss Solskjaer, who has lifted them into the top four since he took over from the beleaguered Jose Mourinho, sacked in December following a 3-1 drubbing at Anfield.
In his spell of more than 26 years as manager at Old Trafford, Alex Ferguson argued more than once that a meeting with Liverpool, rather than City, was United's true derby.
It is a feeling that still holds sway among the club's fans, even though City have risen to win the Premier League three times since 2012 and have become the dominant force in Manchester.
"I think you have got to look at the rivalry," said Rob Mager, a supporter for 30 years and the designer for the club fanzine "United We Stand".
"United and Liverpool have been, historically, the two titans of English football. Over the years, Liverpool have been the more worthy rival than Manchester City and it's been a case of familiarity breeding contempt."
The antipathy between these two northwest cities, 56 kilometres (35 miles) apart, dates back at least to the economic rivalry inspired by the industrial revolution starting in the 18th century.
On the pitch, the mutual dislike between United and Liverpool has grown since the early 1960s, with the clubs taking turns to rule the English game -- racking up 38 league titles and eight European Cups between them.
United have not won the Premier League since 2013 and are realistically out of the running this season but would still love to prevent Liverpool from becoming English champions for the first time since 1990.
- Tough task -
With United taking 25 points from a possible 27 since Solskjaer became their caretaker-manager, Klopp knows this is probably his side's most difficult fixture of the run-in and believes the home team will be a different proposition from the team that surrendered at Anfield.
"It's a big one and we know that it's a difficult one as well," he said, adding that United's attacking players were brimming with confidence.
"They are in a really good moment, really good moment. They are physically strong, they defend well, they attack well."
United have ambitions of their own to finish in the top four, a dream that appeared to have died during the troubled end of Mourinho's reign.
"For them, it's a big game, for us, it's a big game," said Solskjaer. "We want to be in the top four and we know how big this game is for Manchester United, for the staff, for the supporters.
"We're looking forward to another challenge for this team because we want to build this team into one worthy of Manchester United’s history.
"It's another big step if we can do that at home. Tottenham, Arsenal, Chelsea were all fantastic wins away -- now we have to perform at home as well."
Mager is tipping City to win the league, and would rather they were crowned champions.
"Liverpool are our one true rival," he said. "City are more like an annoying little brother. If it was down to me, though, I’d rather neither of them won it. In this season’s title race, I would go for Spurs all day long."