Roberto Mancini's City took top spot temporarily last Saturday after a 1-1 draw at Stoke City only for United to go three points clear with a 1-0 home win over Fulham, where they were lucky to get away with a late penalty shout.
This time City are at home to mid-table Sunderland on Saturday while United visit relegation-threatened neighbours Blackburn Rovers, the only team except for City to win at Old Trafford in the league this term, on Monday.
December's 3-2 defeat rocked United's shaky defence and though the backline has recovered its poise recently with Jonny Evans in especially fine form, City will look to pile on the pressure by beating Sunderland and hope Rovers get a repeat win.
Steve Kean's side lie three points above the drop zone in 16th but even a tough match against a physical side battling to avoid relegation does not faze United forward Javier Hernandez.
"It's a part of the season that all the players want to be involved in," the Mexican told ESPN.
"It's a long season so these final few games are more emotional for everyone, but we have a big chance to win the Premier League again. We're in a great position because it depends on us."
With eight games left and the Manchester duo meeting at Eastlands on April 30, a twist in the title race is almost inevitable and City executive Patrick Vieira has been trying his best to undermine Sir Alex Ferguson's men.
The former France and City midfielder first said United were desperate for calling Paul Scholes out of retirement to fill a hole in their less-than-stellar midfield.
"SOME ADVANTAGE"
Ferguson angrily responded by pointing out that City had welcomed back Carlos Tevez, a player who refused to warm up for a Champions League game in September, disappeared to Argentina and was told by Mancini that he had no future at the club.
Undeterred, Vieira was at it again this week, stating that referees were scared to give penalties at Old Trafford after most pundits agreed that Michael Carrick had tripped Danny Murphy in the dying stages of the Fulham game.
"When United play at home they get some advantage that other teams don't get," Vieira told the BBC.
"I think when you go to United, Madrid, Barcelona or Milan, when the referees referee these kind of games, it's always difficult to go against these kind of teams."
Like Blackburn against United, two other games this weekend affect the top and bottom of the table.
Chelsea are buoyant after their 1-0 win at Benfica in the Champions League quarter-finals and their hopes of guaranteeing a berth in next term's competition will be boosted on Saturday if they win at an Aston Villa side still not certain of safety.
Roberto Di Matteo's outfit are fifth, eight points behind third-placed Arsenal who can consolidate their grip on the final automatic Champions League spot with victory at third-bottom Queens Park Rangers
