The Uruguayan striker struck in each half to take the English side's destiny out of their hands, despite Balotelli's ninth goal in 10 matches that had drawn Mancini's side levelNapoli dealt Manchester City's hopes of reaching the knockout stages of the Champions League a severe blow by recording a 2-1 victory at San Paolo in an exciting, end-to-end Group A match.
Edinson Cavani was the home hero with goals in either half. He recorded the opener after 20 minutes from a corner, his flicked header poorly defended by Aleksandar Kolarov on the post, before Mario Balotelli struck back with a tap-in after the half-hour.
The winner came just after the break when the Uruguayan put away a sumptuous side-footed finish from Andrea Dossena's low pass, to seal a result that sees Napoli leapfrog City in the standings, one point ahead of the Premier League leaders going into the final matchday.
The Citizens will now need to overturn Bayern Munich in their last group game and hope that bottom side Villarreal can upset the odds by recording their first points of the league phase.
City started the match in commanding form and came close when Mario Balotelli curved a shot wide from the edge of the area, but let their concentration slip a little after 10 minutes when Marek Hamsik was allowed space to meet a cross from the right – the visitors were lucky that the Slovak headed straight at Joe Hart.
The home side, buoyed by their first chance, then nearly carved out a beautiful goal. On a furiously fast counterattack, Ezequiel Lavezzi steamed forward in from the left, played a glorious one-two with Cavani, but fired just wide.
Napoli seized the initiative by notching the opener in awkward style. After Hart touched over the bar a rasping 30-yard effort from Gokhan Inler, Cavani met the resulting corner just short of the near post with a flicked header, which then took touches off both the flailing Kolarov and Hart to bounce in.
City looked rattled as the Italians settled down, backed by a vociferous crowd, to defend deep and frustrate the Premier League leaders. But their sitting back backfired when Salvatore Aronica fluffed a clearance, passing it straight to Silva in the box. The Spaniard’s shot was parried by Morgan De Sanctis but Balotelli was on hand to tap in the simplest of finishes on the rebound.
A few minutes later the same scene nearly repeated itself when Kolarov sped past Silva on the left, picking the ball up from him on his way, and aimed a powerful effort at De Sanctis, whose block went loose, but Cavani was back in his box to get there before Edin Dzeko and clear.
After the break, Napoli came out with fire in their bellies. Andrea Dossena slipped into space on the left, supplied by Lavezzi, and then cut a pass back into the area, where Cavani dispatched a neat finish past the slow-to-react Hart to restore the hosts’ lead and renew Mancini’s headaches.
Lavezzi had another bite of the apple a minute later, Hamsik having found some space and attemped to release him. His marker, Vincent Kompany, slipped to allow the Argentine to race into the area, but Hart stood firm to block his strong shot and keep the visitors within reach.
With City scrambling, Cavani nearly turned provider for the killer goal when he produced a sublime crossfield pass from deep, even while being brought down by Kompany, to find Hamsik. The Slovak took advantage of a slight deflection off the defender to jink past and shoot low, but his effort was just slightly too wide and it came back off the post.
Immediately after, Balotelli finally broke Napoli’s defensive line to find himself one-on-one with De Sanctis, but the keeper reacted smartly to deflect his shot, to the striker’s clear frustration.
The home side then pelted back upfield, with Maggio this time breaking into the box and bearing down on Hart, but the impressive keeper provided too big a barrier for the wing-back to seal the win.
The game had become frantic, and City pushed forward again with the substitute Samir Nasri loose in the inside-right channel, but the Frenchman’s cross that sat up invitingly was headed over by Balotelli.
City threw everything they had at the Italians but there was no repeat of the home leg's last-minute miracles and they now stare down the barrel of elimination.