Tottenham bounced back from their horror show against Wigan with a fine display in the 3-1 win over Maribor in the Europa League. Spurs know a much bigger test awaits them at the Etihad Stadium, where they suffered an agonising 3-2 defeat last season, when Defoe almost put Spurs ahead in the final minute before City's last-gasp winner.
Defoe thinks this season's memorable 3-2 win over City's neighbours Manchester United - their first at Old Trafford since 1989 - proves the team can upset the odds at the home of the champions on Sunday. "If you win at United, you can win anywhere and not just in England, anywhere in Europe," Defoe told Spurs TV Online.
"They are one of the biggest clubs in the world and to go there and play how we did in the first half, that performance was unbelievable. The second half was a little different, but you get that at Old Trafford. If we can do the same at City it would be fantastic."
So far this season Roberto Mancini has failed to get his team playing the enterprising football that won them the title last year. The Italian's team have won just one of their last four games and they stand on the brink of exiting the Champions League after a winless start to the competition.
Spurs defender Jan Vertonghen believes this could be a good time to face City's squad of illustrious stars.
"City have been struggling a bit with their confidence and we are strong in away games. We can hurt them on the break," the Belgian said.
"We want to win there and we're capable of it. Why not? City are one of the best teams in the Premier League but with our pace we can hurt anybody, so we're hopeful of getting a good result."
Tottenham manager Andre Villas-Boas sounded a note of caution when discussing the prospect of claiming a vital win in Manchester, however.
He said: "They had an amazing start last year and then a dip towards the end. It can go the other way round for them. A team with such talent and ability is always in a position to bounce back."