It's a fixture that could prove decisive in the Premier League title race, as Man United visit neighbours Man City, leading last season's champions by three points after 15 games.
City remain unbeaten in the league this term and unbeaten on home soil in the top flight since December 2010, giving Mancini's side an edge with most punters heading into this titanic meeting.
Before tuning in for live and exclusive commentary on talkSPORT 1089/1053AM, take a few minutes to read through our selection of this afternoon's key battles, the likely line-ups and remember that you can let off some steam before the game by leaving a comment down below...
Vincent Kompany v Robin van Persie
This is precisely the type of occasion that Sir Alex Ferguson had in mind when parting with £24m for a 29-year-old. Robin van Persie is the Premier League's joint top scorer with ten goals, forcing Wayne Rooney into a deeper role and presumably keeping Vincent Kompany awake with worry last night. Man City's captain endured a difficult start to the season with City conceding four goals in two surprisingly shaky opening matches. If the Belgian international performs as well as he did at Stamford Bridge, in Rafa Benitez's first game as Chelsea manager, Van Persie could be in for a frustrating afternoon. It's the battle most neutrals are looking forward to the most and symbolises City's strength in defence and United's impressive attack.
Yaya Toure v Darren Fletcher
Fletcher started on the bench for Man United against Cluj in midweek, suggesting the Scotland international will be tasked with softening Yaya Toure's inevitable midfield influence. Last season, Park Ji-sung returned from obscurity to perform a similar role, but failed as Toure bossed proceedings from a deeper position in City's narrow 1-0 victory, a result that cost Fergie the title. The absence of Anderson, Valencia and Nani means Michael Carrick should provide Fletcher with added support, in a packed Man United midfield.
Carlos Tevez v Rio Ferdinand
There is no love lost between Tevez and his former employers, with the rampaging forward laying claim to three goals and several high profile spats against the Red Devils since leaving in 2009. He is City's top scorer this season and must be relishing the prospect of tormenting his veteran ex-team-mate, buoyed by home support. By contrast, Ferdinand failed to marshal a back four that shipped three first-half goals at relegation threatened Reading last weekend, and will need to count on his vast experience (plus some improved concentration) to make up for a distinct lack of pace against superior opposition.
The last time these two sides met on 9 December was in 2006, when Man United beat City 3-1 in the Premier League at Old Trafford. Wayne Rooney, Louis Saha and Cristiano Ronaldo scored for the home side, while Bernado Corradi grabbed a late consolation for City.
Man City (4-2-3-1)
Hart, Zabaleta, Kompany, Nastasic, Maicon, Barry, Toure, Silva, Nasri, Tevez, Aguero
Man United (4-2-3-1)
De Gea, Rafael, Ferdinand, Evans, Evra, Fletcher, Carrick, Scholes, Young, Rooney, van Persie
How do you see this top-of-the-table clash going? Let us know by leaving a comment below...