Adebayor returned to action following a three-match suspension to help Spurs earn a 3-1 win over Panathinaikos on Thursday night, while Defoe also found the net.
Tottenham won seven of the eight games the duo started together last season, but Harry Redknapp was not a fan of the partnership as he preferred to play Rafael van der Vaart behind a lone front man.
Andre Villas-Boas continued that policy at the start of the current campaign with Clint Dempsey in the hole, but the Portuguese now seems wedded to the idea of Adebayor and Defoe playing together up front in a 4-4-2 system.
When asked whether the partnership was up there with the best in the Premier League, Friedel, who has played with some prolific strikers in his time, said: "Absolutely. When we have played with two up front, Jermain has really thrived on it, as he can save his energy for when he is inside the box.
That is when it really matters for us. "Last season the system we played was slightly different, with Rafael van der Vaart just behind a lone forward, while at the beginning of this year injuries meant we didn't have the chance to play with two up front, especially at home.
"Jermain always plays on the shoulder of the defender so if a team want to push high up the pitch, he will always keep them honest. "The goal he scored against Panathinaikos was just on-side but he is always right on the edge so defenders have to keep an eye on him." Last night's victory was a nervy affair, but Defoe's 13th of the season, and an own goal from Orestis Karnezis, helped the Londoners qualify.
The win was not enough for them to leapfrog group leaders Lazio, however, meaning Spurs will be unseeded for the second round draw when it takes place in two weeks' time. Last year Redknapp belittled the importance of the tournament, describing it as a "punishment", but Villas-Boas is determined to lift the cup that he won in 2010 with Porto.
Villas-Boas has played a largely first-choice team in the Europa League, giving the likes of Friedel, Gareth Bale and Aaron Lennon a taste of European football and the American stopper is happy that his manager is taking the competition seriously.
"Unlike last year, it's clear that the manager wants to win it," Friedel said. "You can tell that by team selection. Every time we put a very strong team on the pitch and he has not mixed his words at all. "He wants to try to win the competition.
So we are going to take it very seriously." Spurs could move ahead of Chelsea in to third if they maintain their good form on Sunday with a win over sixth-place Everton at Goodison Park. Having played alongside him for Belgium, Jan Vertonghen knows how difficult it will be to shackle Everton dangerman Marouane Fellaini, but he is still confident that Tottenham can return from Merseyside with a win.
"Fellaini is one of the big players in the Premier League," Vertonghen said. "He does amazing. He's a very difficult player to play against. He is strong in the air and with his feet. "He is their most important player and it will be difficult to play him. "But the way we have played the last three games in the Premier League, we can beat anyone and that is what we will be going for."