Only Bayern Munich have escaped from the east of Manchester without a beating this season, and Blackburn Rovers will be the latest team to try and change that after their initial FA Cup third-round tie with City at Ewood Park ended in a 1-1 draw.
The hosts are understandably seen as the big favourites for the clash, but just how will boss Manuel Pellegrini play things ahead of the big Premier League tests to come?
With a potential return for a City favourite from the bench, here's the team he could pick:
It's firmly back to domestic cup duty now for Costel Pantilimon, who has lost the Premier League place that he claimed over Joe Hart at the back end of last year.
The Romanian can also be expected to start next week's dead rubber of Capital One Cup semi-final second leg at West Ham, and although this clash will have more riding on it, he is unlikely to come under too much pressure and will be expecting a morale-boosting clean sheet at the very least.
The gloves will be passed back to Hart for Saturday's league meeting with Cardiff, though.
Micah Richards returned to the bench at Newcastle, and he could earn a start here as Pablo Zabaleta is given a rest and Dedryck Boyata's City career continues to fade away.
The return of Richards will strengthen Manuel Pellegrini's defence at such a crucial period of the season, and the Chilean might well look to rely on skipper Vincent Kompany here as he bids to earn a safe passage through to the fourth round.
Joleon Lescott and Gael Clichy played in the first match at Ewood Park, and both could return to the side here, too.
Yaya Toure limped off at Newcastle, and it is in City's best interests to leave him out here and hope that he'll recover in time for Cardiff on Saturday.
In his place, Javi Garcia could slot in alongside the virtually ever-present Fernandinho, with both taking it in turns to get forward and join in the attack.
Further forward, the injury to Samir Nasri at St James' Park will have rocked City given the fine form of the Frenchman, and with David Silva now required to be protected ahead of the challenges to come, James Milner and Jesus Navas could be used from the start. Portuguese youngster Marcos Lopes might be introduced from the bench depending on the state of the game.
For the fifth successive game in 2014, Alvaro Negredo and Edin Dzeko are set to start a match upfront together, and both are fresh from scoring in the win at Newcastle.
It would take a brave man to back against one or both scoring again here, but they are certain to have one eye on the bench and the potential return of a player who has to be regarded as their club's first choice forward.
Sergio Aguero could be fit to return to the squad here, and with a start considered highly unlikely, a comeback from the bench in place of one of these two could well be witnessed in the second half.
As mentioned in the previous slide, this clash could see the return of Sergio Aguero after eight matches out with the hamstring injury he picked up in the win over Arsenal.
Should everything go to plan for Pellegrini, he'd love to introduce his fellow South American for around half an hour or so of this clash, with an eye on more of an involvement against Cardiff in the Premier League on Saturday.
Youngster Marcos Lopes is also likely to be seen from the bench, and he could make an impact given the absence of the injured Samir Nasri.
David Silva, Martin Demichelis and Aleksandar Kolarov could also be on call, if needed.
The absence of Toure ensures that Fernandinho and Javi Garcia will have to take turns getting forward in this formation, with the underrated James Milner also handed a chance to impress in an attacking role.
The back four are all experienced enough to deal with the threat posed by Rovers, whilst Edin Dzeko might view the possible presence of Sergio Aguero on the bench as a challenge.
If he and Alvaro Negredo click again, then there's a spot in the FA Cup fourth round up for grabs.