Tottenham failed to show the spirit and quality that Tim Sherwood had demanded following the defeat to Chelsea in the English Premier League, with the North London side falling 3-1 to Benfica in the first leg of their last 16 tie at White Hart Lane.
There were no such problems for the likes of Valencia, FC Porto, Lyon and AZ Alkmaar, however, while Real Betis stunned rivals Sevilla 2-0 in the Seville Derby. Juventus will have to find at least one goal in the second leg after conceding a 1-1 draw to fellow Serie A side Fiorentina.
All the talk going into the Benfica game was about Sherwood calling his players out, repeatedly saying that a lot of the members of the squad were playing for their Tottenham careers.
Well, if he expected a public rollicking would wake the Tottenham players up, he was wrong, as Benfica showed their class in earning a big lead heading into the second leg.
Rodrigo opened the scoring for the Portuguese league leaders, stroking the ball home wonderfully in the 29th minute, before defender Luisao headed home from a corner in the 58th minute to make it 2-0 to the away side.
Christian Eriksen pulled one back for Tottenham with a brilliant curling freekick, but Benfica as good as put the tie to bed with Luisao completing his brace, latching onto a rebound after an initial save from Hugo Lloris off Ezequiel Garay.
In Turin, Mario remember-me? Gomez scored a vital away goal, coming off the bench, to cancel Arturo Vidal's third-minute strike.
Juventus battered Fiorentina in the first half, striking the woodwork on a couple of occasions, forcing saves from goalkeeper Neto, but the away team held on and struck decisively 11 minutes from time to give them the slight advantage going into the second leg in Florence next week.
The Seville Derby was supposed to go Sevilla - the home team's - way, but it was Betis, rooted to the bottom of La Liga and seemingly destined for the drop, that found their mojo as Leo Baptistao, in the 15th minute, and Salva Sevilla, thirteen minutes from time, helped their side to a 2-0 win.
Lyon pretty much booked their place in the quarterfinals with a 4-1 thumping of Viktoria Plzen, who conceded four consecutive goals - two of them Guieda Fofana - after taking an early lead. Former Fulham, Tottenham and Sunderland midfielder Steed Malbranque was the star for the French side, with the 34-year-old notching up three assists.
FC Porto grabbed a 1-0 advantage of Napoli with Chelsea and Arsenal target Jackson Martinez scoring the only goal of the game in the 57th minute, while Valencia eased to a 3-0 away victory over Ludogorets.
Basel and Salzburg played out a goalless draw in Switzerland as Aron Johansson gave AZ a 1-0 win in the first leg over Russian side Anzhi Makhachkala.
Results: Lyon 4-1 Viktoria Plzen, AZ Alkmaar 1-0 Anzhi Makhachkala, Ludogorets 0-3 Valencia, Juventus 1-1 Fiorentina, Sevilla 0-2 Real Betis, Porto 1-0 Napoli, Basel 0-0 Salzburg, Tottenham 1-3 Benfica.