With Robbie Keane serving a three-match ban, Ramos opted to start the game with Darren Bent alongside Dimitar Berbatov.
The move looked to have paid off when Pascal Chimbonda fired the home side into the lead in controversial circumstances on the stroke of half-time as he appeared to use his hand to direct the ball past Andreas Isaksson.
City substitute Rolando Bianchi grabbed an equaliser midway through the second half and it looked as if Tottenham had thrown away another victory at White Hart Lane.
But when City midfielder Stephen Ireland was shown a red card for a reckless 82nd-minute challenge on Young-Pyo Lee, it was left to substitute Defoe to steal the headlines when he grabbed the winner 60 seconds later.
Tottenham started the game brightly and could have opened the scoring on nine minutes when Berbatov played Bent through on goal, but his shot was kept out by the legs of Isaksson.
The home side went close to breaking the deadlock again on 12 minutes when Berbatov's ball fell to Steed Malbranque, but the Tottenham winger's shot deflected off Richard Dunne and flew inches past the post.
Tottenham finally got their just rewards when they scored on the stroke of half-time.
Jermaine Jenas played his free-kick into Berbatov who back-heeled the ball towards goal for Chimbonda, who looked as if he used his hand to direct the ball past Isaksson and into the back of the net.
City equalised on 61 minutes when Martin Petrov's corner fell to Bianchi. He pulled away from Bent and flashed a header past Paul Robinson and into the corner of the net.
The game completely changed on 82 minutes when Ireland was dismissed for a two-footed challenge on Lee.
The home side made the extra man count just one minute later when Malbranque's shot came back off the post and Defoe was on hand to fire the rebound home.