Former European champions Steaua Bucharest stunned UEFA Cup holders Valencia by dumping the Spanish champions out of the competition in a penalty shootout on Thursday.
Valencia coach Claudio Ranieri could find himself out of a job on Friday after the club said they would hold a board meeting to discuss the Italian's future at Mestalla.
Valencia's hope of retaining their league title have faded after a dismal run but asked after this defeat whether he would resign Ranieri replied: "No. I never surrender, I always carry on fighting."
Apart from Parma's impressive 2-0 victory in Germany over VfB Stuttgart to send the Italians through, it was a bad night for former winners with Schalke 04, Ajax Amsterdam and Feyenoord all going out.
Sporting, whose Alvalade stadium in Lisbon will host the final on May 18, had their victory over Feyenoord overshadowed by crowd disturbances in Rotterdam which twice halted the match.
UEFA sanctions are likely to be imposed on the Dutch club after Sporting goalkeeper Ricardo was hit by a firework in the first half which brought a five-minute delay.
Referee Florian Meyer then took the players off for 20 minutes in the second half after Sporting's Rui Jorge had been struck by an object thrown from the crowd following Liedson's goal. Sporting won the match 2-1 to go through 4-2 on aggregate.
Valencia took a two-goal lead to Romania's Steaua Bucharest but were pegged back by two second-half strikes from midfielder Andrei Cristea, restored to the starting lineup by Italian coach Walter Zenga at the behest of the club's main shareholder Gigi Becali.
"I was right when asking for Cristea to play from the start," Becali told reporters. "I paid a lot of money for him so I think I'm permitted to ask the coach [Zenga] to allow my favourite player to start a match."
With no goals in extra time, it took a miss by Italian striker Marco Di Vaio to hand the Romanians a 4-3 spot-kick win.
Steaua will now play another Spanish side in Villarreal in the last 16 after last season's semi-finalists overcame Dynamo Kiev.
Marco Marchionni and Andrea Pisanu struck in extra time to send Parma through to a meeting with Sevilla, who went through thanks to a stoppage-time goal from Adriano that sealed a 2-1 aggregate victory over Panathinaikos.
Parma, twice UEFA winners in the 1990s, had been reduced to 10 men late in normal time after Paolo Cannavaro's two-footed foul on Stuttgart's Kevin Kuranyi.
But Marchionni struck eight minutes into the first half of extra time after twice exchanging passes with Alberto Gilardino, then Pisanu added the second in the 117th minute, following up on the rebound after Timo Hildebrand could only palm away a Simplicio shot.
AJ Auxerre's long-serving coach Guy Roux described his side's 3-1 victory over Ajax, for a 3-2 win over the two legs, as "more than a miracle".
"It's just a great game we played," said Roux after an 88th minute header by substitute Lionel Mathis sealed a last 16 tie with fellow French Ligue 1 side Lille.
Bonaventure Kalou opened the scoring for Auxerre and Benoit Cheyrou put them back in front after youngster Ryan Babel had equalised for Ajax shortly before the break.
In another upset, Shakhtar Donetsk stunned 1997 winners Schalke 04 with a 1-0 win in Gelsenkirchen that gave the Ukraine side a 2-1 aggregate victory.
Nigerian striker Julius Aghahowa, whose goals in a 2-0 Champions League victory over Barcelona landed Shakhtar a UEFA Cup spot, thumped home a powerful drive on 21 minutes to dump the Bundesliga high-flyers out of Europe.
Shakhtar will now meet AZ Alkmaar after the Dutch side survived a real fright at home before ending German second division side Alemannia Aachen's fairytale run.
Alkmaar, trailing to Erik Meijer's first-half strike, turned the match around with goals from Dutch international Barry van Galen and Joris Mathijsen in the last half hour to win 2-1 on the night and the same score on aggregate.
Former England captain Alan Shearer scored his seventh UEFA Cup goal of the season for Newcastle United who overcame Dutch side Heerenveen 2-1 at St James' Park for a 4-2 aggregate success. The English Premier League side's reward is a second knockout round tie with Olympiakos Piraeus after the Greek side disposed of Sochaux.
CSKA Moscow, 2-0 up from the first leg, coasted through after holding Benfica to a 1-1 draw in Portugal. Sergei Ignashevich gave the Russian side the lead with substitute Azar Karadas levelling on the night.
Real Zaragoza, Middlesbrough and Partizan Belgrade also went through.