Shane Long also found the net as Saints kept their Europa League qualification bid alive, strolling home against a City lineup distracted as much by fears for their individual futures as thoughts of the Champions League.
Kelechi Iheanacho struck twice for the visitors, but Manuel Pellegrini’s largely reserve line-up wilted with precious little resistance on the south coast.
City boss Pellegrini made eight changes from Tuesday’s goalless Champions League semifinal first leg draw with Real Madrid, gearing up for Wednesday’s return at the Bernabeu.
The Chilean duly exposed the shortcomings in his squad building at the Etihad outfit however, with many on show rightly fretting that Pep Guardiola will wield the axe on arrival at the club this summer.
Pellegrini’s rotation backfired spectacularly with City yet to close out a top-four finish to guarantee Champions League football next term.
But the former Real Madrid boss can justifiably lambaste the limp performances of a host of experienced hands, who could easily be shipped out by Guardiola before next season.
Fabian Delph, Fernandinho, Wilfried Bony, Pablo Zabaleta and Aleksandar Kolarov could all be expecting the worst on this evidence.
An entirely different City altogether will face Real in Madrid on Wednesday, and now Pellegrini must hope this resounding defeat carries no significance into Europe.
City’s vast changes ripped out any rhythm, and after a meandering opening the hosts took full advantage.
Pablo Zabaleta had to scramble a recovery to deny Long, before Hart and Mangala were both forced to clear testing crosses from Tadic.
Steven Davis’ neat through-ball set Long tearing into the inside-right channel, and his low first-time strike only just swept past Hart’s near post.
Despite the warning shots City should have opened the scoring, Raheem Sterling’s poor finish letting down Kelechi Iheanacho’s persistence.
The Nigeria forward picked Virgil van Dijk’s pocket on the touchline, drove into the box and cut back a smart ball to the onrushing Sterling.
The former Liverpool winger blasted his shot straight down the middle of the goal however, leaving Fraster Forster with a showy but expected save.
Then Saints changed the game, Tadic laying on two goals in three minutes to turn the tie.
First the Serbia playmaker latched onto Cuco Martina’s angled ball and flicked a cross that Long slid through Hart’s legs.
Then Tadic slid through a fine ball to send Mane clear, and he finished neatly past Hart.
The goals toppled an already-wobbling City. The visitors were overrun in midfield from the outset, spending the majority of the first half chasing shadows.
Mane, Davis and Tadic overwhelmed Fabian Delph and Fernandinho too often to credit the duo’s berths in a squad still eyeing Champions League glory.
City wrestled their way back into the contest just before the break however, Martina diverting a poor clearance straight to Iheanacho.
The 19-year-old nodded home the gift, to claim City a foothold they hardly deserved.
Southampton quickly shrugged off Iheanacho’s goal after the break however, with Mane pouncing twice more to complete a smart hat-trick and sink the woeful visitors.
First Mane slotted home on the rebound after Van Dijk’s header from Davis’ corner had crashed against the bar, then the 24-year-old slid the ball past Hart after another inch-perfect through-ball from Tadic.
Iheanacho struck again for the visitors with a fine finish after Jesus Navas’ smart ball, but the damage was long since done by a group of nearly-men whose futures at City are most certainly in doubt.