Plzen beat defending champions Atletico Madrid to top their qualifying group and are now heavy favourites to progress past the high-flying Italians after late goals from Stanislav Tecl and Frantisek Rajtoral built on Vladimar Darida's first-half opener.
Anzhi Makhachkala recovered from a goal down to defeat Hannover 3-1. Hannover took a 22nd-minute lead through Szabolcs Huszti but Samuel Eto'o drew Anzhi level soon after and Odil Ahmedov put the hosts ahead on 46.
Eto'o then spurned the chance to make it 3-1 in the 57th minute when his spot-kick was saved by Ron-Robert Zieler, but Anzhi were still able to secure a two-goal lead to take to Germany for the second leg thanks to Mbark Boussoufa.
Levante put aside their poor domestic form to claim an impressive 3-0 victory over 10-man Olympiacos. Goals from Pedro Rios, Jose Barkero and Obafemi Martins earned Juan Ignacio Martinez's men a notable scalp.
Goals by Toby Alderweireld and Ricardo Van Rhijn guided Ajax to a 2-0 victory over 10-man Steaua Bucharest at the Amsterdam ArenA.
Oscar Cardozo's second-half strike was enough to give Benfica a 1-0 victory at Bayer Leverkusen.
Two goals for Lazio from Libor Kozak as well as three penalties for Borussia Monchengladbach saw a breathless match end with the 10-man Italian club in pole position ahead of the second leg, with the tie poised at 3-3.
Atletico Madrid look to be heading out after they were beaten 2-0 at home by Rubin Kazan. Gokdeniz Karadeniz put the Russians ahead after six minutes before Pablo Orbaiz doubled their advantage in added on time.
Rodrigo Palacio scored twice following his early entrance as a substitute to put Inter Milan in control of their tie against Cluj. Palacio scored 10 minutes after that and added a late second in a 2-0 win.
Oleg Gusev missed a second-half penalty as wasteful Dynamo Kiev played out a 1-1 draw with Bordeaux. The Ukrainian hosts dominated the contest and took a deserved lead through Lukman Haruna, but that was cancelled out within minutes by Ludovic Obraniak.
Fenerbahce held BATE Borisov to a 0-0 draw in Belarus despite playing all bar the first three minutes with 10 men after Raul Meireles was sent off early on.
Juande Ramos' chances of becoming only the second manager to win the Europa League for a third time may have to wait another year after his Dnipro side were beaten 2-0 by Basle at St. Jakob-Park.
Ramos had won the trophy twice before at Sevilla and a third triumph would put him level with Republic of Ireland boss Giovanni Trapattoni. However a first-half goal from Valentin Stocker and a second-half strike from Marco Streller ensured the Swiss side head into next week's second leg at the Dnipro Stadium in control.
A last-minute goal from Glynor Plet gave Genk a precious away goal as they held Stuttgart 1-1 at the Mercedes-Benz Arena. Christian Gentner had fired the hosts ahead before half-time, but Plet struck in stoppage time to level the scores and give his team the advantage heading into the return match in Belgium next week.