Ajax, Lazio and Tottenham suffered first leg defeats as Swansea held Napoli to an impressive goalless draw in the round of 32 of the Europa League on Thursday.
Juventus had no problems in dispatching Turkish side Trabzonspor in their first leg match, while fellow Italian side Fiorentina and Spanish heavyweights Valencia also took leads into the second leg.
In Ukraine, Spurs suffered a 1-0 defeat at the hands of Dnipro Dnipropetrovsk and former manager Juande Ramos, with Yevhen Konoplyanka, the man Tottenham and Liverpool targeted during the January transfer window, scoring the only goal in the 80th minute from the penalty spot.
Jan Vertonghen was adjudged to have brought down the impressive Dnipro striker Matheus inside the penalty box, with Konoplyanka making no mistake with the spot-kick.
Both sides struggled to make a game of it on a difficult pitch, but Roberto Soldado's woes in front of goal continued as the Spanish international missed a sitter early in the first half off a cross from Paulinho.
Tottenham will now have to score a couple of goals in the second leg at White Hart Lane to ensure their progress into the last 16 of the Europa League, with Dnipro knowing a single away goal can put them firmly in the driver's seat.
At the Liberty Stadium, Swansea were much the better side than Napoli, but despite dominating the game - the home side had nearly 70 percent possession, and 8 shots on target to Napoli's one - they could not find the back of the net.
Napoli will now be confident of getting the desired result at home in the second leg, but if Gary Monk's side play anything like they did on Thursday, they are in with a real chance of creating a big upset.
In Turin, there was to be no surprises, as on-loan Southampton striker Dani Osvaldo and Paul Pogba scored for Juventus to give the Italian champions a 2-0 victory over Trabzonspor.
Fiorentina picked up an impressive 3-1 away victory over Esbjerg, thanks to goals from Alessandro Matri, Josep Ilicic and former Liverpool midfielder Alberto Aquilani, with Martin Pusic netting what proved to be a consolation strike. But Lazio did not enjoy much success as they were brought down by Ludogorets, who got their goal through Roman Bezjak for a 1-0 victory.
Valencia moved into the second leg at home with a sizeable advantage, with Eduardo Vargas and Sofiane Feghouli netting late in the game to take a 2-0 lead over Dynamo Kyiv.
Rodrigo Lima was the hero for Benfica, scoring the only goal of the game at PAOK FC, while fellow Portuguese side FC Porto were held to a 2-2 draw at home by Eintracht Frankfurt.
At the Amsterdam Arena, Ajax were thumped 3-0 by FC Salzburg, with all three goals coming in the first half. Jonatan Soriano opened the scoring for the Austrian side via the penalty spot in the 14th minute, after Joel Veltman brought down Alan inside the box.
Sadio Mane made it 2-0 for Salzburg in the 21st minute, before Soriano scored a wonder strike from near the halfway line to add to Ajax's misery.
Results: Anzhi Makhachkala 0-0 Genk; Dynamo Kyiv 0-2 Valencia; Maribor 2-2 Sevilla; Chornomorets 0-0 Lyon; Maccabi Tel Aviv 0-0 FC Basel; Real Betis 1-1 Rubin Kazan; Dnipro 1-0 Tottenham; Juventus 2-0 Trabzonspor; PAOK 0-1 Benfica; Viktoria Plzen 1-1 Shakhtar Donetsk; Esbjerg 1-3 Fiorentina; Swansea 0-0 Napoli; Lazio 0-1 Ludogorets; Liberec 0-1 AZ Alkmaar; Porto 2-2 Eintracht Frankfurt; Ajax 0-3 Salzburg.