Inter Milan, Parma and Roma were all dumped out of the Uefa Cup on a night to forget for Italian clubs in Europe.
By contrast, Spain enjoyed a memorable evening as all four sides - Barcelona, Alaves, Rayo Vallecano and Celta Vigo - booked their passage into the last eight.
The performance of the night was from Alaves who triumphed 2-0 on the night and 5-3 on aggregate over Serie A giants Inter in the intimidating atmosphere of the San Siro.
Jordi Cruyff and Ivan Tomic were the goal heroes for the Spanish underdogs, who moved a step nearer to the first trophy in the club's 80-year history.
The Uefa Cup was Inter's last chance for honours this season after they were eliminated from the qualifying stage of the Champions League by Helsingborgs, knocked out of the Italian Cup by Parma and dropped out of contention for the Scudetto.
Alaves' win sets up a an all-Spanish quarter-final tie with Rayo Vallecano, who beat Bordeaux 2-1 to clinch a 6-2 aggregate victory.
Serie A leaders Roma crashed out to Liverpool after they won at Anfield but failed to overturn their 2-0 first-leg defeat in the Olympic Stadium.
Parma completed an unwanted hat-trick for Italy when they went out on away goals to PSV Eindhoven despite a brave fightback.
Already trailing 2-1 from the first leg, the Italians left themselves with a mountain to climb after going in two down at the break. Two goals from Yugoslavia striker Savo Milosevic and Johnnier Montano's injury-time winner gave Parma a 3-2 victory but it was too little too late.
Barcelona's Luis Enrique put AEK Athens to the sword in front of a meagre 15,000 crowd at the Nou Camp as the Catalan club cruised into an all-Spanish quarter-final clash with Celta Vigo.
The Spain international scored a hat-trick as the Greek side crumbled following Michalis Kapsis' 29th minute dismissal for a professional foul on Patrick Kluivert.
Celta needed a late winner from Alexander Mostovoi against VfB Stuttgart to secure their place in the next round.
With the scores at 1-1 following a goalless first leg, the German side would have gone through on the away goals rule until Mostovoi headed home in the 84th minute.
Vratislav Lokvenc's winner for Kaiserslautern was the only goal over two legs against Slavia Prague. The Czech international striker pounced in the 59th minute to book the German side's passage into the next round where they will face Dutch champions PSV Eindhoven.
Nantes narrowly failed to claw back a three-goal aggregate deficit as Porto ended French interest in this year's Uefa Cup and set up a showdown with Liverpool.
Trailing 3-1 from the first leg, the French side found themselves further behind on 35 minutes after a superb solo goal by Renivaldo Pena.
Nantes fought back but two second-half strikes from sub Marama Vahirua and Sylvain Armand in the space of seven minutes were not enough to force extra time.