Brazil striker Nilmar grabbed a dramatic injury-time winner in Villarreal's 3-2 victory at Bayer Leverkusen but English sides Liverpool and Manchester City sank to first-leg defeats in the Europa League's last 16 on Thursday.
Nilmar scored moments after coming off the bench to put Villarreal 2-1 ahead in the 70th minute in Germany, before racing clear to slot home the winning goal four minutes into added-on time.
Liverpool, a three-time winner of Europe's second-tier competition, slipped to a 1-0 defeat at Braga - one of three Portuguese teams to open the last 16 with wins.
City fared even worse, losing 2-0 at Ukrainian side Dynamo Kiev to leave the big-spending Premier League club with a mountain to climb in next week's second leg at Eastlands.
FC Porto won 1-0 at CSKA Moscow in a match between two former winners, and Benfica rallied to beat visiting French side Paris Saint-Germain 2-1 to make it a superb night for Portuguese teams.
In the other three matches, Spartak Moscow defeated Ajax 1-0 away, Dutch champion FC Twente thrashed 2008 champion Zenit St. Petersburg 3-0, and Scottish side Rangers produced a resolute defensive display to hold PSV Eindhoven to a 0-0 draw away.
All eight second legs take place on March 17.
Nilmar came on for Giuseppe Rossi, who had canceled out Michal Kadlec's 33rd-minute opener with a goal in the 42nd that took the Italy striker to a competition-high seven goals this season - level with Porto striker Falcao.
The substitute robbed Kadlec and danced through the Leverkusen defense to score his first and after Gonzalo Castro equalized two minutes later, Nilmar secured the win by running away from the Leverkusen defense to slip the ball past goalkeeper Rene Adler.
Braga inflicted a first defeat in 12 European games for Liverpool this season when Osorio Alan converted a 17th-minute penalty, conceded by Sotirios Kyrgiakos for a clumsy foul on midfielder Mossoro.
"The way we started, we were terrible," Liverpool manager Kenny Dalglish said. "But I think at 1-0, we still have a chance."
Braga left back Silvio struck a volley against the crossbar midway through the first half and it took the introduction of record signing Andy Carroll to spark Liverpool, which was without talismanic captain Steven Gerrard, into life.
Dirk Kuyt and Kyrgiakos both fired over within a minute of each other, while Braga defender Kaka was lucky to avoid a red card for elbowing Carroll in the face late on.
Veteran striker Andrey Shevchenko finished from close range in the 25th to put Kiev ahead against City in freezing conditions in the Ukraine capital.
Oleg Gusev then volleyed home in the 77th to leave sluggish City, which started with top scorer Carlos Tevez on the bench but was otherwise at full strength, on the verge of elimination.
"We made mistakes for both goals," said City manager Roberto Mancini. "We can't do that in a game like this."
Colombia midfielder Fredy Guarin scored Porto's 70th-minute winner with a crashing effort from distance against CSKA, putting the 2003 champions and runaway Portuguese leaders in a strong position ahead of the second leg.
"We had problems in the first half but we proved to be the (better) team in the second and won," Porto coach Andre Villas Boas said through a translator. "The encounter is not over. CSKA is a tough team and can score in a week."
Peguy Luyindula opened the scoring for PSG at Benfica but the hosts recovered through goals by Maxi Pereira and Franco Jara either side of halftime to take a slim lead to France.
Alex's second-half strike secured Spartak a smash-and-grab win at Amsterdam ArenA and Luuk de Jong's double helped Twente to an easy victory over Zenit. Denny Landzaat scored Twente's other goal.