LONDON ENGLAND - FEBRUARY 16: A detailed view of the FA Cup sponsored by Eon at the Leyton Orient FA Cup Media Day at Matchroom Stadium on February 16 2011 in London England. (Photo by Dean Mouhtaropoulos/Getty Images)
Contrasting fortunes heading into the game then. United, buoyed by Champions League progression and with hopes high of a treble with one hand already clasped around the Premier League trophy.
City on the other hand go into the game on the back of a miserable evening at Anfield, where the performance as much (perhaps moreso) was far more of a concern. They also saw captain and talismanic figure Carlos Tevez limped from the field, out of action for the best part of a month with a hamstring injury.
In many ways the season really does start here. The work put into getting the side into this position with a chance of silverware and Champions League qualification should not be viewed lightly, but in the short-term, the next month could have far reaching ramifications for the long-term.
Better news emerged late in the week for City though as Micah Richards was passed fit and will likely be risked at right-back, with another returning player - Pablo Zabaleta - returning on the left, hopes far higher than of being able to thwart United's threat out wide.
The absence of Tevez leaves Roberto Mancini with a tricky decision, and one which likely boils down to a choice between Edin Dzeko and Mario Balotelli as the replacement for the Argentinean. Neither come into the game with much form to speak of and the decision may well come down to how the midfield is set up.
The likely scenario is that the trusted trio of Yaya Toure, Nigel de Jong (so badly missed against Liverpool) and Gareth Barry will be in place with David Silva and one other - seemingly a choice between the industry and work rate of James Milner and the more offensive threat of Adam Johnson. An unlikely option would be Shaun Wright-Phillips, ho has a history of success against United (and Patrice Evra in particular) and would likely mean Dzeko getting the nod. You have to think though - given Mancini's talk this week - that Balotelli, as unpredictable as he is, will get the start, and if so it will be Johnson or Milner opposite to the floating presence of Silva.
As much as Carlos Tevez has at times struggled against United, a result no doubt due to an over-keeness to succeed and get one over his former employers, his loss is a tremendous one. Whilst there are key elements throughout the side, Tevez's presence and influence are impossible to replicate and it is more a case of hope rather than expectation in terms of the front line producing without him.
Rooney's absence will be a blow to United, his suspension coming when he is producing the best form of his sketchy season and the expectation is that it will mean a lone striking role for Dmitar Berbatov, possessor of 22 goals this season, who Alex Ferguson has often deployed when one or both of Rooney and Chicharito have been absent. As mentioned earlier, the threat United possess out wide - pick from Ryan Giggs, Ji-Sung Park, Antonio Valencia and the fast-developing Nani is well documented. This is an area where City will be heavily tested with the likes of Michael Carrick and Paul Scholes able to get quick balls out to them. In defence, the presence of Rio Ferdinand will be important: with him in the side they concede just 0.62 goals per game. Without him, it jumps to 1.05.
The approach of both sides will be interesting to see. Even with last season's Carling Cup ties, games have always been played on a home and away basis, where initiative is ceded accordingly. Not so this time with the game being staged on neutral territory at Wembley Stadium. Do both sides approach cautiously, almost an away-style performance, cagey early and allow the game to develop? Or do both sides try to come out quickly and strike early?
Crucially, both sides possess exceptional home records (less so on the road), and have been able to hammer home advantages gained early. United have won 17 of 22 (Premier League) games when scoring first, City 15 of 19. Yet City have won just 1 of 9 when they fall behind and United only 3 of 7 when the opposition scores. Equally, when leading at half-time, City have won 12 of 14 with no defeats, whilst United have on 15 of 18, with just one loss. One interesting stat is that when drawing at half-time, United are unbeaten (winning 3 and drawing 7) whilst in comparison City have won 4, drawn 5 and lost 3 when level at the break. Sobering figures indeed should City concede first and/or trail going in at half-time.
It is a difficult game to call. Clearly there is not a huge amount in terms of separation between the two sides, and lest we forget prior to the defeat at Liverpool the garden was rosy following the 5-0 demolition of Sunderland. In recent times though, United have possessed that edge that has seen them gain the upper hand; call it resolve, strength of will or just plain old experience of having continually been in and emerged victorious from similar situations.
As of yet, and despite the strides made by City in recent times, when they have needed to take that step forward they have yet to have done so and until they do there will always be a question mark hanging over them. Defeat on Saturday and it could have a knock-on effect to league form at the worst possible time. Win however and not only ill it seal a place in the FA Cup final (and ninety minutes from silverware) but would provide a huge fillip for the remaining league fixtures.
Time to step up.