While City maintained its two-point lead over United with a 3-0 victory over Stoke, its second-place rivals routed Fulham 5-0 at Craven Cottage.
Such emphatic victories have been the norm for big-spending City this season, but for United it was the biggest in three months.
"It was very impressive, we've not scored as many as we'd like to but we'd been playing well," United winger Ryan Giggs said. "The second part of the season we always kick on and put in performances and that's pleasing."
Arsenal had more difficulties at Aston Villa, with Yossi Benayoun's late goal securing a 2-1 victory for his fifth-place side.
Liverpool is two points behind Arsenal after Charlie Adam missed a penalty kick in a 0-0 draw at Wigan. Luis Suarez featured for Liverpool a day after receiving an eight-match ban — on hold pending any appeal — for racially abusing United defender Patrice Evra.
United had failed to win on its past three visits to Craven Cottage but Danny Welbeck's fifth-minute opener, capitalizing on lax defending, was an early sign that the run would come to an end.
The lead was doubled when a cross from Giggs was headed home by Nani in the 28th before the 38-year-old midfielder became the first player to score in all 20 Premier League seasons.
A shot deflected off Philippe Senderos and looped into the net three minutes before half time.
An industrious performance from Rooney was capped in the 88th when the England striker fired home from 30 yards.
But United saved the best until last as Berbatov netted his 50th goal for United with a nonchalant backheel from Antonio Valencia's cross.
"In the second half we took our foot off the gas but we were always in control and we knew we were going to win the game," Rooney said.
MADRID (AP) — Atletico Madrid and Villarreal's woeful seasons got worse Wednesday as the topflight clubs were eliminated from the Copa del Rey by third-tier teams on home soil, leading Villarreal to fire coach Juan Carlos Garrido.
Albacete beat Atletico 1-0 to reach the last 16 with a 3-1 aggregate victory, while Pablo Infante scored a pair of second-half goals for Mirandes to win 2-0 at Villarreal and advance 3-1 overall.
Villarreal wasted no time in dismissing Garrido after the latest setback to its awful season, in which it is sitting 17th in the league and exited the Champions League after losing all six group stage games.
Atletico coach Gregorio Manzano could be next to leave.
"Until I'm informed of the opposite, I'll continue to answer questions professionally, in my role," Manzano said.
Real Betis was the another topflight club eliminated from the domestic cup competition, going out on away goals following a 2-1 win over Cordoba that left the series tied 2-2.
Other teams to advance on Wednesday included 23-time cup winner Athletic Bilbao, Racing Santander, Osasuna, Levante, Malaga and Real Sociedad. Defending champion Real Madrid, Espanyol, Sevilla and Mallorca all won their fourth-round matches on Tuesday to advance.
Barcelona holds a 1-0 lead over third-tier Hospitalet ahead of their match on Thursday, when Valencia welcomes Cadiz after the pair played to a scoreless draw in the first leg.
Claudio Marchisio and Fabio Quagliarella had the best of Juve's chances while Mauricio Isla came close to breaking the deadlock for Udinese.
In contrast there were plenty of goals in the other Serie A matches. Diego Milito broke his goalscoring duck to help Inter Milan beat Lecce 4-1, while Atalanta also won 4-1 against Cesena. Napoli did even better, humiliating Genoa 6-1.
Catania came back from two goals down to draw 3-3 at Parma.
Juventus remains unbeaten and is now level on points with Milan heading into the winter break. Despite that, goalkeeper Gianluigi Buffon insists the team is still not thinking of the Serie A title.
"It was a good game and I think in the end a draw was the fairest result," Buffon said. "We're still unbeaten and that's a fact we're proud of, nobody would have ever thought of being in this place.
"What's our aim for 2012? It's not the title but we're aiming to qualify for the Champions League."
Udinese, which lost its perfect record at the Stadio Friuli, is two points behind Juventus and Milan.
PARIS (AP) — Big-spending Paris Saint-Germain will take a three-point lead into the French league's winter break after grinding out a scrappy 1-0 win at Saint-Etienne and taking advantage of its three main rivals dropping points.
PSG's cash-rich Qatar owners have spent $107 million on players this season and coach Antoine Kombouare's team is under intense pressure to win the title for the first time since 1994.
After 19 games, they are halfway there, and Christmas will have a warmer glow after Montpellier, Lille and Lyon all failed to win on Wednesday.
PSG's goal came after Nene floated over a corner in the 32nd minute and midfielder Mathieu Bodmer's header hit the post and bounced back off goalkeeper Stephane Ruffier's hand and into the net.
"You need a bit of luck, but also a lot of mental strength," PSG defender Zoumana Camara said. "That's why we got the result tonight."
Montpellier led 2-1 but then conceded three goals in eight minutes as it lost 4-2 at Evian.
Although Lille moved within one point of Montpellier after drawing 4-4 at home to 10-man Nice, it surrendered the lead three times in an absorbing game which saw Nice equalize in the fourth minute of injury time. Lyon, meanwhile, was full of confidence after winning its last four league games but lost 1-0 at Valenciennes and missed the chance to overtake both Lille and Montpellier.
FRANKFURT, Germany (AP) — Borussia Moenchengladbach knocked out title holder Schalke from the German Cup with a 3-1 win on Wednesday, while fourth-tier Holstein Kiel stunned Mainz 2-0 to reach the quarterfinals for the first time in 68 years.
Schalke finished the match with nine men after red cards for top scorer Klaas-Jan Huntelaar in the first minute of the second half and Jermaine Jones in injury time.
Rising star Marco Reus scored two goals for Moenchengladbach and played a role in another as the surprise team of the season continued its strong run through two domestic competitions.
Stuttgart beat Hamburger SV 2-1 on two goals from striker Cacau.
Kiel had already eliminated two second-division teams to make the third round. The team from northern Germany went ahead after six minutes on an own goal from Anthony Ujah and Steve Mueller secured the victory with a goal in the second half.
Hertha Berlin defeated Kaiserslautern 3-1 to reach the last eight for the first time in four years. Hertha won under interim coach Rainer Widmayer after firing Markus Babbel on Sunday.