Having yet to win a match in Group D, City are rock bottom with two points, yet victories over Real and in their final match away to group leaders Borussia Dortmund could see them squeeze into the last 16, depending on results elsewhere.
"It's always special to play against a club like Real Madrid. Personally, my connection with Atletico Madrid gives it an additional kick - but there's no difference in how much I want to win this match," Aguero told City's website.
"Never defeating Real when I was with Atletico was a real regret for me - Atletico haven't succeeded in beating them for many years - but I did get to score against them even if we never managed a win.
"Wednesday night will hopefully break that run for me."
It looks a tall order, but a 5-0 home victory against Aston Villa on Saturday, when Aguero netted twice, sent them top of the Premier League and raised spirits in time for the visit of Jose Mourinho's side who could go through if they better Ajax's result against Dortmund.
City have only won three of their 10 matches in the Champions League since qualifying last season and failure to beat Real would eliminate them at the group stage for the second consecutive season although Aguero said they were determined to fight until the end.
"We should never give up," the Argentine said. "Where there's a will, there's a way, right?
"Of course, it's harder now because we're not just relying on ourselves but also on the other teams' results.
"What we mustn't do is leave the pitch with any regrets and be content knowing that we have given our all. This club deserves nothing less and our supporters deserve as much, too."
BIG VICTORY
Like City, Real are also buoyed by a big league victory, having thrashed Athletic Bilbao 5-1 at the weekend.
France striker Karim Benzema, back after a thigh muscle injury, was in fine form in that victory, curling in a sweetly struck shot for Real's third goal and unselfishly setting up Mesut Ozil for their fourth.
"We don't like talking about individuals, but he [Benzema] had an outstanding game," former Real striker Emilio Butragueno, now a club director, told Spanish television.
"His movement in attack was fabulous and he scored a great goal," Butragueno added. "It was a delight to see him playing that way after his injury."
Mourinho, hoping to lead Real to the 10th European crown that has eluded them since 2002, also has Sami Khedira back after injury. The German international, who came on in the second half of the Bilbao game and netted Real's fifth, will likely rejoin Xabi Alonso in central midfield.
Mourinho will become the youngest coach to take charge of 100 Champions League matches on Wednesday and only the fifth manager to reach the milestone after Carlo Ancelotti, Arsene Wenger, Ottmar Hitzfeld and Sir Alex Ferguson.
The 49-year-old Portuguese made his debut in Europe's elite club competition in February 2002 when he was in charge at Porto in a game they lost 1-0 to Real Madrid at the Bernabeu.
His record in 99 matches with Porto, Chelsea, Inter Milan and Real is 54 wins, 25 draws and 20 defeats, with 166 goals scored and 85 conceded.
Probable teams:
Manchester City: 1-Joe Hart; 5-Pablo Zabaleta, 4-Vincent Kompany, 33-Matija Nastasic, 22-Gael Clichy; 8-Samir Nasri, 14-Javi Garcia, 42-Yaya Toure, 18-Gareth Barry; 16-Sergio Aguero, 32-Carlos Tevez.
Real Madrid: 1-Iker Casillas; 17-Alvaro Arbeloa, 3-Pepe, 4-Sergio Ramos, 5-Fabio Coentrao; 14-Xabi Alonso, 6-Sami Khedira; 21-Jose Callejon, 10-Mesut Ozil, 7-Cristiano Ronaldo; 9-Karim Benzema.
Referee: Gianluca Rocchi (Italy).
