While Roberto Mancini's side are flying high in the Premier League two points clear of Manchester United at the top, the same cannot be said of their Group A campaign in which they have one point from two games.
"We have four games left and to have a chance of progressing we need to beat Villarreal. We need 10 points," Mancini told reporters.
Aguero missed Saturday's 4-1 league win over Aston Villa with a groin injury and other leading players were rested after international duty, but the Argentine is fit to face a Spanish side he knows well from his La Liga days at Atletico Madrid.
"He will be ready for Villarreal," said Mancini who also has Spain midfielder David Silva's inside knowledge to tap into.
"I think he [Silva] is one of the best players in the world. He improved a lot in the last year."
City's top scorer this season with eight league goals, Aguero is likely to partner Edin Dzeko up front while Mario Balotelli serves the final match of a three-game ban and Carlos Tevez remains ostracised as he faces disciplinary action.
Tevez's alleged refusal to come on as a second-half substitute in the last Champions League game against Bayern Munich detracted attention from what was a poor collective performance in a 2-0 defeat.
The competition's debutants were held to a 1-1 draw at home to Napoli in their opener and they blamed first-night nerves, which they will not be able to do at the Etihad stadium this week against visitors who have lost both group games.
Villarreal, who have never beaten an English team in eight Champions League matches and have failed to score in seven of those, go into the game with injury concerns.
Coach Juan Carlos Garrido has been forced to call up three players from the youth side as five of his first-team squad are out, including Brazil striker Nilmar who is recuperating from knee surgery.
Former Spain international Marcos Senna and fellow midfielder Javier Camunas picked up muscle strains in Saturday's 0-0 La Liga draw at Getafe, joining Nilmar, forward Marco Ruben and defender Angel in the treatment room.
Garrido said after Saturday's game the team had shown signs of improvement following a disappointing start to the domestic campaign, when they have recorded only one win in seven outings.
"On the one hand, we enjoy these matches, but on the other we suffer competing against great players," he said.
"For us the two games against Manchester are like a knockout match because qualification for the next phase is at stake."
Bayern lead the group on six points with Napoli second on four.
Manchester City: 25-Joe Hart; 22-Gael Clichy, 5-Pablo Zabaleta, 4-Vincent Kompany, 2-Micah Richards; 21-David Silva, 42-Yaya Toure, 18-Gareth Barry, 19-Samir Nasri; 10-Edin Dzeko, 16-Sergio Aguero.
Villarreal: 13-Diego Lopez; 12-Cristian Zapata, 2
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