Former UEFA Cup winners Schalke paid the price for leaving Spanish striker Raul at home as they slumped to an embarrassing Europa League defeat to HJK in Helsinki.
Raul was reportedly rested by the Bundesliga side but with a confirmed offer from Blackburn and speculation mounting about his future, more questions will be asked after his side's 2-0 loss.
Teemu Pukki opened the scoring in the 18th minute for the Finnish side and added a second nine minutes into the second half, leaving HJK in a strong position when they head into the second leg next week.
Double UEFA Cup winners Sevilla were stunned by two Jan Schlaudraff goals as Hannover held on to record a 2-1 first-leg win over the Spaniards in Germany.
The 28-year-old opened the scoring in the sixth minute and despite Frederic Kanoute equalising on 37, Schlaudraff added his second moments after the restart to restore his side's lead.
There was another shock as former finalists Roma fell to the only goal of the game by Slovan Bratislava's Martin Dobrotka in the 80th minute, giving the Italian giants a major challenge in next week's second leg.
Portugal's Sporting Braga, losing finalists to Porto in May, could only draw 0-0 at home to Swiss side Young Boys.
And former UEFA Cup winners PSV Eindhoven were also held to a goalless draw by Ried in Austria.
Former England number one Scott Carson could not help his new club Bursaspor hold onto a half-time lead against Anderlecht.
Brazilian Gokcek Vederson put the Turks in front but second-half strikes from Jonathan Legear and Milan Jovanovic gave the visitors a 2-1 win.
Former European champions Steaua Bucharest eased towards the group stage with a 2-0 home win over CSKA Sofia, with goals from George Galamaz and Brazilian striker Leandro Tatu.
Former European champions Red Star Belgrade were beaten 2-1 in Serbia by Rennes, for whom Jonathan Pitroipa and Victor Montano cancelled out Brazilian Cadu's early penalty.
Juan Pastore failed to score on his debut for Paris St Germain as they swept aside Differdange 4-0 in Luxembourg, while Lazio were the biggest winners of the night as two from Djibril Cisse lifted them to a 6-0 home win over Rabotnicki of Macedonia.
Two late goals from Brazilian substitute Elias gave Atletico Madrid a 2-0 win over Portugal's Vitoria Guimaraes. Elias replaced Silvio in the 65th minute, shortly after the visitors' Joao Paulo had been shown a red card.