Diego Forlan was Atletico Madrid's last gasp hero against Galatasaray, Anderlecht put Athletic Bilbao to the sword, while Hamburg just about progressed at the expense of PSV Eindhoven.
Juventus knocked out fellow European heavyweights Ajax, Lille's draw in Fenerbahce ensured their progression and Rubin Kazan joined them courtesy of a stalemate against Hapoel Tel-Aviv.
An enthralling night of football in the Europa League also saw Marseille saunter into the last 16 as they beat FC Copenhagen 6-2 on aggregate.
Substitute Diego Forlan struck a last-gasp winner as Atletico Madrid stunned Turkish giants Galatasaray at the Ali Sami Yen stadium to progress.
Forlan had started the game on the bench but he was called into action at the end of the first half when Sergio Aguero was forced off with a facial injury, and the Uruguayan ended up being his side's hero.
He struck in the 90th minute just as the tie looked set to go to extra time with the two sides locked at 1-1 - the same scoreline from the first leg.
Earlier, Kader Keita had quickly cancelled out Simao Sabrosa's 62nd-minute opener for Atletico, before Galatasaray were reduced to 10 men in the 80th minute when Caner Erkin was sent off.
After a goalless first half Antonio Lopez's throw-in was headed on by Jose Manuel Jurado and Simao stole in to fire past former Atletico custodian Leo Franco in the home net.
Atletico's lead lasted just three minutes though before they were undone for the second time in successive matches by Keita. Galatasaray captain Arda Turin's cross to the far post was perfect for Keita, and his header was too good for Sergio Asenjo.
It was left to Forlan to steal a dramatic win at the death when we fired home from inside the area.
Mbark Boussoufa enjoyed a starring role as Anderlecht breezed into the next round with a comfortable 4-0 second-leg win over Athletic Bilbao.
La Liga outfit Athletic were left kicking themselves after only drawing 1-1 in the first leg at home and they were made to pay as the Belgians moved through to face Dutch side PSV Eindhoven in the next round.
Goals by Romelu Lukaku, a Mikel San Jose own goal, Boussoufa and Jonathan Legear sealed their passage in impressive style as Joaquin Caparros' side limped out of the competition.
After Mbark Boussoufa fed the ball in from the right, Lukaku seized on the opportunity in just the fourth and sent his left-footed shot from close range past Gorka Iraizoz.
Legear then crossed the ball in and while no Anderlecht striker was on the end of it, San Jose managed to nod the ball into his own net.
After the remainder of the half petered out, the Belgians sealed their progression as the impressive Boussoufa headed home from six yards to make it 4-1 on aggregate.
The Basques' only response was a series of silly fouls before, in the 68th minute, Legear made it 4-0 on the night with a right-footed drive from the edge of the box.
Marseille cruised through to the last 16 of the Europa League after recording a convincing 6-2 aggregate victory over FC Copenhagen.
The French outfit had done most of the hard work in the first leg, where three late goals earned them a 3-1 win in Denmark, and they completed the job with minimum fuss with an identical scoreline to set up a showdown with Benfica in the next round.
Hatem Ben Arfa, who also struck in the first leg, broke the deadlock just before the interval at a blustery Stade Velodrome and Bakari Kone added two more goals in the final half-hour.
Ailton's late effort was the scantest of consolations for a well beaten FC Copenhagen.
Hamburg came from behind to progress to the last 16 on away goals following a pulsating contest at PSV Eindhoven.
PSV swiftly brought the last-32 contest level with a second-minute strike from Ola Toivonen and Balazs Dzsudzsak netted a long-range free-kick to put the hosts in front on aggregate before half-time.
But Hamburg netted a valuable away goal in the first minute after the restart when Mladen Petric's deft chip went in and Dzsudzsak was then dismissed for two yellow cards in a matter of moments, handing the initiative to the visitors.
Guy Demel was sent off for Hamburg, but the Bundesliga side then levelled on the night from a Piotr Trochowski penalty after 78 minutes to go 3-1 up on aggregate.
Danny Koevermans headed in after 89 minutes but Hamburg held on to set up a last-16 clash with Anderlecht.
Juventus stood firm as Italy's only representatives in the Europa League by holding Ajax to a goalless draw at the Stadio Olimpico to complete a 2-1 aggregate victory.
The home side came the closest to breaking the deadlock in the first half when Mohamed Sissoko hit the post with a header, but they did not need a goal to progress to the last 16.
Ajax lacked incision in attack as they failed to trouble the Juve goalkeeper Alex Manninger.
Rubin Kazan were given no cause for alarm in a second-leg stroll to earn a 3-0 aggregate victory over Hapoel Tel-Aviv and a Europa League last-16 clash with Wolfsburg.
Having all but sealed their passage in the first leg, during which Aleksandr Bukharov scored twice and Sergei Semak also found the target, Rubin were content to sit back in Tel-Aviv.
Hapoel struggled to muster a meaningful effort on target as they limply exited the competition, but Rubin will be required to step up a gear in the next round against a Wolfsburg side who thrashed Villarreal.
Lille reached the last 16 as Adil Rami's header proved the difference against Fenerbahce.
The Turkish giants had looked set to progress once Emre's strike had given them the advantage on away goals, but the Ligue 1 side applied plenty of pressure and were finally rewarded with five minutes to go.
Rami netted from close range to secure a last-16 clash with Liverpool.