City are smarting from another miserable Champions League outing, which saw them beaten by Borussia Dortmund and knocked out of Europe to become the first English side to finish the group stage without a victory.
City drew with Everton last time out in the league and lie three points behind United in second place. They remain the only unbeaten team in the division.
United also suffered a midweek disappointment in Europe, and though their defeat to CFR Cluj had no bearing on their progress in the Champions League, it was a result that did little for their confidence heading into the derby.
Sir Alex Ferguson's team have won their last three in the Premier League, most recently coming from behind to beat Reading in a frantic encounter at the Madejski. Few would doubt United's attacking pedigree. Even fewer would doubt the holes in their defence this season.
Here are five battles to watch on Sunday.
Jonny Evans won't need reminding what happened at Old Trafford last October. United were hit for six by City, and the defender had a disastrous afternoon that culminated in a red card.
Evans will need to be at his best to marshall Sergio Aguero, who has scored five times in City's last five home games and will be looking to embarrass the United defence with his late runs and fast feet inside the box.
With Nemanja Vidic not quite ready to return from injury, Rio Ferdinand seems likely to pass Aguero duties over to Evans, who is better suited to cope with Aguero's pace.
Sir Alex Ferguson's midfield is a mystery only he knows the answer to. Should he trust Darren Fletcher with defensive duties—as he did at Reading—the returning Scot could very well be tasked with subduing David Silva.
City's most potent creative force is himself returning from injury, but Roberto Mancini is very much hoping Silva will be fit to start on Sunday.
If he does, Fletcher will have his work cut out tracking Silva's runs and making sure he doesn't have room to run into between United's midfield and their defence.
Wayne Rooney was everywhere against Reading. It's almost as if he has a free role in this United team, and that makes him very difficult to track for the opposition defence.
Rooney is likely to serve as an advanced midfielder against City. He'll be charged with linking play to Robin van Persie, and City's Yaya Toure is probably the player he'll be in most competition with in those areas of the pitch.
Toure and Rooney share a combative style and athleticism that should make for a meaty battle. Both will look to carry the ball forward if given a chance and neither is afraid of putting his body in the way of an opponent's progress.
Carlos Tevez never stops moving. Should he start in the derby, Tevez will be looking to get down the channels either side of Jonny Evans and Rio Ferdinand and drag the United defence all over the place.
Assuming Evans is marshalling Sergio Aguero, Ferdinand will be the man tasked with tracking those runs and trying to stay as close to his old teammate as possible.
He'll need maximum concentration and the support of his deep-lying midfielders and fullbacks to succeed in this task, because Tevez will fancy his chances in a straight sprint and won't be afraid of running at Ferdinand every time he gets the ball.
United will have chances at the Etihad and Robin van Persie will almost certainly test Joe Hart in City's goal. The Dutchman is the joint leading scorer in the Premier League with 10 goals and needs the merest sniff to summon an effort on target.
Hart, meanwhile, didn't have the best of months in November. He made a few high-profile mistakes and City manager Roberto Mancini appeared to issue a public warning over his form—suggesting his place was not assured in the City starting lineup.
If Sunday's derby is a game of small margins, the battle between Van Persie and Hart could very well decide its outcome.