Emmanuel Adebayor continued to inspire Tottenham, netting a brilliant brace to pull his side past Dnipro Dnipropetrovsk as Napoli ousted Swansea in their round of 32 tie of the Europa League.
Sevilla and Real Betis set up a can't-miss-it derby clash after coming through their respective opponents, as Porto snuck through on away goals. Ajax and Shakhtar Donetsk, who would have started the knockout rounds as two possible title winners, were knocked out by FC Salzburg and Viktoria Plzen respectively.
Lazio also suffered an early exit, while Juventus cruised into the next round courtesy a 4-0 aggregate victory over Turkish side Trabzonspor.
At White Hart Lane, Spurs, starting the second leg 1-0 down, looked on the brink of being knocked out after Roman Zozulya headed home a freekick from Ruslan Rotan three minutes into the second half.
Roberto Soldado, desperate for a goal, thought he had levelled things up in the second leg, after firing home off a through ball from Christian Eriksen, only to see the dreaded offside flag being raised by the assistant referee.
However, Tottenham would find their momentum towards a remarkable comeback via Eriksen, who curled home a brilliant freekick to make it 2-1 on aggregate.
Zozulya went from hero to villain, after being shown a straight red card for an off-the-ball incident on Jan Vertonghen, with Adebayor taking centre-stage soon after.
Why-on-earth-am-I-not-the-first-name-on-the-teamsheet Eriksen was the creator of Spurs' second goal, firing in a low cross for Adebayor to slot home in the 65th minute, with the Togo international then completing his brace four minutes later courtesy a nice finish.
Dnipro, now 3-2 down, pressed forward, with Yevhen Konoplyanka forcing outstanding saves from Hugo Lloris, but Spurs held on to setup a clash with Benfica in the last 16, after the Portuguese side eased past PAOK 4-0 on aggregate.
In Naples, goals from Lorenzo Insigne, Gonzalo Higuain and Gokhan Inler, the last two coming in the final 12 minutes, saw Napoli advance past Swansea 3-1, with the English Premier League side getting their consolation goal through Jonathan De Guzman.
Napoli face Porto in the pre-quarterfinals, after the Champions League regulars edged past German side Eintracht Frankfurt on away goals following a thrilling tie which ended 5-5 on aggregate.
Joining Porto in the next round are Basel, Lyon, AZ Alkmaar, Fiorentina and Valencia, after they got past Maccabi Tel Aviv, Dynamo Kyiv, Liberec, Esbjerg and Chornomorets Odesa respectively.
A mouthwatering derby clash lies in wait in Spain with Sevilla getting past Maribor 4-3 on aggregate and Betis easing past Rubin Kazan 3-1 on aggregate, following a 2-0 second leg victory.
"I think [the derby with Betis] will be the game with the most attention, but for us the most important thing is to stay on track," Sevilla skipper Ivan Rakitic was quoted as saying by UEFA's official website. "We really want to beat Betis.
"We have got a chance to show our fans we are a very strong and united team, and derbies are great to play in. We are going to take it one game at a time, trying to keep going all the way to the final."
Results: Rubin Kazan 0-2 Real Betis (1-3 aggregate), Napoli 3-1 Swansea (3-1), Sevilla 2-1 Maribor (4-3), Shakhtar Donetsk 1-2 Viktoria Plzen (2-3), Ludogorets 3-3 Lazio (4-3), Salzburg 3-1 Ajax (6-1), Basel 3-0 Maccabi Tel Aviv (3-0), Eintracht Frankfurt 3-3 Porto (5-5, away goals), Genk 0-2 Anzhi Makhachkala (0-2), Valencia 0-0 Dynamo Kyiv (2-0), Benfica 3-0 PAOK (4-0), AZ Alkmaar 1-1 Liberec (2-1), Fiorentina 1-1 Esbjerg (4-2), Lyon 1-0 Chornomorets Odesa (1-0), Trabzonspor 0-2 Juventus (0-4), Tottenham 3-1 Dnipro Dnipropetrovsk (3-2).
