London - Benfica snatched a 2-2 draw at sloppy Manchester United to reach the Champions League last 16 and leave the three-times winners with work to do, while Inter Milan ambled through before even playing and Bayern Munich also progressed with ease on Tuesday.
Real Madrid had already booked their first knockout round berth but secured top spot in Group D in style with a 6-2 home thrashing of competition whipping boys Dinamo Zagreb despite playing several reserves.
Ajax Amsterdam all but sealed their passage in the other group game with a 0-0 draw against Olympique Lyon while Manchester City risk bowing out like the French in next month's last set of matches after a 2-1 loss at last-16 hopefuls Napoli.
United went behind at Old Trafford to an early Phil Jones own goal and although little-used Dimitar Berbatov and midfielder Darren Fletcher puts the hosts in front, poor defending let in Pablo Aimar for Benfica's precious equaliser.
Alex Ferguson's men now need a point next month from their final Group C game at Basel to go through with the Swiss side requiring a famous win over the English champions after a 3-2 victory at Otelul Galati on Tuesday.
"It was a bit freakish to be honest, an own goal and a bad kick out by (goalkeeper) David de Gea," Ferguson, who was without the injured Wayne Rooney and suspended Nemanja Vidic, told Sky Sports.
"It's a cruel game at times and it was cruel for us tonight. We were missing a few players but with the squad I've got I've got no complaints about that."
The result also meant United, who have reached the final in three out of the last four years, are unlikely to top the group and gain a favourable last-16 draw even if they beat Basel given leaders Benfica are at home to pointless Galati.
Inter, the 2010 winners, reached February's first knockout round after Group B rivals Lille revived their chances of going through with a 2-0 win at CSKA Moscow in freezing conditions in the early game.
A 1-1 draw at Trabzonspor meant Inter also sealed top spot with the Turks, Lille and CSKA all in the running for the second qualification spot.
Bayern, beaten in the final by Inter two seasons ago, powered through and made sure of finishing top of Group A with a routine 3-1 home win over struggling Villarreal in which Franck Ribery scored twice.
Edinson Cavani grabbed a brace too as Napoli put themselves in pole position to follow the Germans into the last 16 and left English Premier League leaders City trailing by a point.
The world's richest club, making their Champions League debut, must beat Bayern in Manchester in two weeks' time and hope eliminated Villarreal do them a favour by at least drawing with Napoli in Spain.
"We will enjoy this beautiful moment, we always knew right from the first day that we could do it," Uruguay striker Cavani, nicknamed the Matador, told Mediaset Premium.
Karim Benzema and Jose Callejon also both scored twice as Real steamrollered Dinamo at the Bernabeu without the likes of Iker Casillas and Cristiano Ronaldo.
Jose Mourinho, who won the trophy with Porto and Inter, has seen his nine-times winners take a maximum 15 points from their first five games and score 16 goals, one more than woeful Dinamo have conceded.
In the same group, Ajax can make plans for the last 16 after their goalless draw at Lyon left them three points ahead in second spot but with a vastly superior goal difference and the same head-to-head record as Remi Garde's team.
Lyon's only hope of qualifying for the knockout stages for a ninth straight time is a massive win at Dinamo on December 7 while hoping Real continue the party at the Amsterdam Arena - not an altogether impossible scenario.
Teams in Groups E-H play their penultimate matches on Wednesday with Chelsea, Bayer Leverkusen, Arsenal, Olympique Marseille, APOEL Nicosia and Zenit St. Petersburg all having a chance of progressing with a game to spare.
Heavyweights AC Milan and Barcelona meet at the San Siro with both sides already through but fighting over first place
Tuesday's Champions League results (home team denoted first):
Napoli (ITA) 2 (Cavani 17, 49) Manchester City (ENG) 1 (Balotelli 33)
Bayern Munich (GER) 3 (Ribery 3, 69, Gomez 23) Villarreal (ESP) 1 (De Guzman 50)
Trabzonspor (TUR) 1 (Altintop 23) Inter Milan (ITA) 1 (Alvarez 18)
CSKA Moscow (RUS) 0 Lille (FRA) 2 (V. Berezutsky 49-og, Sow 64)
Otelul Galati (ROM) 2 (Giurgiu 75, Antal 81) Basel (SUI) 3 (F. Frei 10, A. Frei 14, Streller 37)
Manchester United (ENG) 2 (Berbatov 30, Fletcher 59) Benfica (POR) 2 (Jones 3-o.g, Aimar 60)
Real Madrid (Benzema 2, 66, Jose Callejon 6, 49, Higuain 9, Ozil 20) Dinamo Zagreb 2 (Beciraj 81, Tomecak 90)
Lyon (FRA) 0 Ajax (NED) 0
Zenit St Petersburg v Apoel Nicosia - 19:00
BATE v Plzen - 20:00
Bayer Leverkusen v Chelsea - 21:45
Shakhtar Donetsk v FC Porto - 21:45
Arsenal v Borussia Dortmund - 21:45
Valencia v Genk - 21:45
AC Milan v Barcelona - 21:45
Marseille v Olympiacos - 21:45