Arsenal put on an impressive display to defeat Serie A giants Napoli at the Emirates Stadium.
Aaron Ramsey got the home side up and running after just 14 minutes, turning home a cross from Naitland-Miles.
Lucas Torreira capped off an impressive half for Unai Emery's side with a deflected effort from distance.
Carlo Ancelotti's men were unable to claw their way back into the encounter and will now have tough task of overturning a 2-0 deficit in the second leg.
Valencia will take a healthy advantage to next week's second leg after defeating Villarreal 3-1 on Thursday night.
Goncalo Guedes gave the away side a crucial away goal after opening the scoring after six minutes, before parity was restored through Santi Cazorla's penalty in the 36th minute.
The visitors left it late to seal the win as Daniel Wass made it 2-1 on 90 minutes before Guedes completed his brace three minutes later.
Benfica laid down their intentions for a spot in the final four after defeating Eintracht Frankfurt 4-2 at the Estádio do Sport Lisboa e Benfica.
Joao Felix stole the show by bagging a hat-trick, while the youngster also got the assist for Ruben Dias' goal.
There is a small bit of hope for Frankfurt, who grabbed two away goals through Luka Jovic and Goncalo Paciencia.
Chelsea needed a late goal from Marcos Alonso to secure a 1-0 win over Slavia Praha on Thursday evening.
FThe Blues are only side left yet to suffer a defeat in the tournament.
