The chinks in Inter Milan's armour were exposed again as Tottenham Hotspur beat the holders 3-1 in Champions League Group A and all three teams able to secure last-16 qualification flopped on Tuesday.
Manchester United were the only group leaders who could not guarantee qualification this week but they took a big leap towards the first knockout round thanks to goals by Darren Fletcher, Gabriel Obertan and Bebe in a 3-0 win at Bursaspor.
Valencia prevailed 3-0 against Rangers to leapfrog their opponents into second in Group C.
Rafael van der Vaart, suspended when Inter beat Spurs 4-3 two weeks ago, sent White Hart Lane mad in the return with a first-half goal after good work by Luca Modric but the Dutchman was substituted at the break with a nagging injury.
Peter Crouch made sure it was an unhappy return to England for his former Liverpool boss Rafael Benitez when he slid in for the second on 61 minutes after Gareth Bale, hat-trick hero at the San Siro, again showed stunning speed to whip in the cross.
Red-hot Samuel Eto'o bagged his seventh goal of the group stage but Roman Pavlyuchenko converted another Bale pass a minute from time as Tottenham went top on head-to-head record.
In the other group game, Dutch champions Twente Enschede boosted their slight hopes of progressing with a 2-0 win at Werder Bremen.
Barca's Lionel Messi cast his magic spell on the Champions League yet again with a well-taken opener on the half hour but a flap by Victor Valdes allowed Claudemir to level for Copenhagen just a minute later. Rubin Kazan and Panathinaikos drew 0-0.
Lyon were blown away by Benfica's verve and Fabio Coentrao's brace before a spirited fightback from 4-0 down almost levelled matters but second-placed Schalke 04 could not take full advantage with a 0-0 stalemate at Hapoel Tel Aviv.
The other four groups play on Wednesday.