Pep Guardiola's side have reinstated themselves as title favourites in the eyes of many with the best winning run any team has managed in the Premier League this season, and they will be looking to keep that going against a Villa side that has not been in top-flight action for almost three weeks.
Manchester City have shown more than anyone else in recent weeks how a level of consistency can be so effective in such a topsy-turvy and tightly-contested Premier League season.
Guardiola's men were as low as 15th at one stage in the campaign and have only occupied a top-four spot for less than a week throughout 2020-21 so far, yet they suddenly find themselves with the title race effectively in their hands.
The Citizens would have been the happiest of the spectators as two title rivals Liverpool and Manchester United played out a drab goalless draw at Anfield prior that victory, which allowed them to close the gap on leaders United to only two points, with City also boasting a game in hand.
In all competitions Man City's winning run now stands at eight matches stretching back more than a month, while they are unbeaten in their last 15 outings.
Key to their revival after a slow start has been their defensive improvement; Guardiola's men shipped seven goals in their opening three games of this season across all competitions, but have since shipped just nine in their next 25.
Man City have let in just one goal during their ongoing five-match winning streak in the league and have now kept nine clean sheets in their 17 top-flight outings this season - their best ever tally at this stage of a campaign in the competition's history.
Unsurprisingly, they also boast the best defensive record in the league overall with only 13 goals conceded from their 17 games, but in Aston Villa they come up against the second-best.
Admittedly the Villans have played at least two fewer games than anyone else in the division due to COVID-related postponements, but their tally of 16 goals conceded from 15 games is still respectable, while they have also scored as many goals as Man City this season in two fewer games.
Wednesday's match will be the first time Villa's senior side have played since New Year's Day following an outbreak of coronavirus in their squad, with the club's only outing since then seeing their valiant youngsters knocked out of the FA Cup by a strong Liverpool side.
Incidentally, Villa's last first-team outing was another trip to Manchester as they fell to a 2-1 defeat at the hands of Manchester United, and they have not picked up a victory since beating Crystal Palace on Boxing Day.
In fairness, they have faced Chelsea, Manchester United, Liverpool and now Man City in succession since then, and given Man City's form in general, and indeed in this fixture, Dean Smith may not be expecting too much from their trip to the Etihad.
Villa have lost 14 of their last 15 Premier League visits to Man City, including each of the last 10 in a row by a 33-4 aggregate scoreline, while home or away they are winless in nine meetings with Man City across all competitions, losing eight of those.
However, there is more reason to be optimistic this time around than on many of their previous visits, with Villa still sitting in the top half despite their games in hand. Indeed, should Villa go on to win those three games in hand then they would be right up there alongside Man City in the title mix.
Smith's side have been particularly good away from home with five wins from eight Premier League games on the road this term - as many as they had managed in their previous 49 such outings.
Manchester City Premier League form: DWWWWW
Manchester City form (all competitions): WWWWWW
Aston Villa Premier League form: WDWWDL
Aston Villa form (all competitions): DWWDLL
Sergio Aguero is again expected to miss out following a period of self-isolation after coming into contact with someone who had tested positive for COVID-19.
The Argentine, who has scored 10 goals in just seven starts against Villa including a hat-trick last season, could be in contention if he returns a negative test in time, but he is unlikely to be thrown straight back in regardless.
Gabriel Jesus led the line against Palace but failed to get amongst the goals, so Guardiola could look to shuffle his pack a little up front with the likes of Ferran Torres, Phil Foden and Riyad Mahrez pushing for starts after sitting out on Sunday.
Rodri, Joao Cancelo and Benjamin Mendy may also be hopeful of coming back into the side, but one player expected to start again is Kevin De Bruyne following his exquisite 100th assist for Man City last time out.
The playmaker has now provided more assists in all competitions than any other Premier League player this season and was withdrawn with 20 minutes to play on Sunday in order to keep him fresh for this match.
The in-form Stones and Ruben Dias will also expect to keep their places, despite the likelihood of Aymeric Laporte recovering from a hamstring injury. Nathan Ake and Eric Garcia could also be available, but Guardiola may view the weekend FA Cup trip to Cheltenham Town as a better opportunity to rest his new first-choice centre-back duo.
Predicting which Aston Villa team they come up against will be an exercise in guesswork for Guardiola given the coronavirus problems the visitors have experienced in recent weeks.
Ten first-team players tested positive, but who those players were and how badly they were affected remains unclear. Every player was affected in some way, though, with the Villa training ground being forced to close for 10 days.
Trezeguet is the only confirmed case and he could miss out, while Wesley is still a long-term absentee too, but the break should have given Ross Barkley the chance to get back up to speed following a thigh injury.
Villa fans will be hoping that Man City-linked Jack Grealish, more than anyone, is available; the talismanic skipper has been directly involved in 12 goals from his 15 Premier League games this season - the most by a Villa player in their first 15 games of a top-flight season since Dalian Atkinson in 1992-93.
Manchester City possible starting lineup:
Ederson; Cancelo, Stones, Dias, Mendy; De Bruyne, Rodri, Gundogan; Mahrez, Sterling, Foden
Aston Villa possible starting lineup:
Martinez; Cash, Konsa, Mings, Targett; Luiz, McGinn; El Ghazi, Barkley, Grealish; Watkins
We say: Manchester City 3-1 Aston Villa
The fact that Man City have conceded the fewest Premier League home goals this season, while Aston Villa have shipped the fewest on the road so far this term suggests that this one might not be a goal-fest.
However, Villa have also scored in all of their away games this season while Man City's four-goal showing against Crystal Palace suggests that they are beginning to rediscover their clinical edge in front of goal.
We can therefore see an entertaining game between two teams that like to attack, but ultimately it is difficult to back against Man City in their current ominous form, particularly after such a disrupted period for Villa.
Top betting tip
Watch the Sports Mole Football Shorts prediction for this game below: