Goran Pandev opened the scoring for Napoli at the Stadio San Paolo with a calm finish past goalkeeper Fabiano to level the score on aggregate, following Porto's 1-0 win in the first leg.
Napoli then had several opportunities to move ahead in the tie, with Lorenzo Insigne having arguably the best opportunity with a close-range header that forced Fabiano into a smart save.
The home side were punished for their profligacy, however, as Porto's two goals in eight second-half minutes secured a quick turnaround, with strikes from forward Nabil Ghilas - who also scored the goal that put Porto through to the last 16 against Eintracht Frankfurt - and winger Ricardo Quaresma took the game away from Napoli.
Napoli forward Duvan Zapata ensured the scores would finish 2-2 on the night with a close-range goal in injury time, but it was not enough to stop Porto progressing.
And Napoli head coach Benitez feels his side needed to show more composure in front of goal.
Speaking to Football Italia, he said: "I think the team played a spectacular game with chances, control and intensity against a side that played with a high defence and we had the opportunities to make the difference.
"We should've finished our chances with more precision and determination. We didn't and that's where the game went wrong.
"Porto had a couple of chances in the first leg, but tonight it was just one-way traffic."
