Italian and English sides endured a terrible evening in the UEFA Cup with AC Milan's defeat being the biggest betting surprise of the evening.
The Rossoneri had been favourites to win the competition only for Werder Bremen to stage a remarkable comeback at the San Siro.
Claudio Pizarro scored twice as the German side hit back from 2-0 down to draw 2-2 and reach the last 16 on away goals after the tie ended 3-3 on aggregate.
Fiorentina also crashed out of the competition, losing 2-1 on aggregate to Ajax after drawing 1-1 in the second leg in Amsterdam while Metalist knocked Sampdoria out.
The one ray of hope for Serie A sides came from Udinese who limped to a narrow 4-3 aggregate success over Polish side Lech Poznan.
However, they had to come from behind before sealing a 2-1 second leg victory thanks to goals by Simone Pepe and Antonio Di Natale.
Premier League sides Tottenham and Aston Villa fielded weakened sides as they lost to Shakhtar Donetsk and CSKA Moscow respectively so Manchester City will be the only English representatives in the last 16 after a Craig Bellamy double sank FC Copenhagen.
Holders Zenit St Petersburg eased through by beating Stuttgart 4-2 on aggregate while Sabri Sariogluto grabbed a last-gasp winner as Galatasaray knocked out Bordeaux in a seven-goal thriller.
Valencia, who won the trophy in 2004, slipped to defeat against Dynamo Kiev on away goals. Kiev's victory set up an all-Ukrainian last 16 tie against Metalist.
Hamburg beat NEC Nijmegen 4-0 while another Dutch side, FC Twente, lost by a smaller margin, a penalty shoot-out after a 1-1 aggregate scoreline, to Marseille.
Meanwhile in the FA Cup, after making seven changes to his starting line-up, Phil Brown saw his Hull City side make it through to the sixth round thanks to a scrappy 2-1 win over Sheffield United.
In cricket, a century from Andrew Strauss helped England reach 301-3 on the first day of the fourth Test against West Indies, while Australia recovered from a poor start to post a total of 254-5 after day one of their first Test against South Africa in Johannesburg.
In golf, Tiger Woods lost 4&2 to Tim Clark to crash out of the WGC Accenture Match Play Championship in the second round.
Elsewhere, Rory McIlroy birdied the last two holes to beat Hunter Mahan while Lee Westwood lost to Stewart Cink, Paul Casey beat Matthew Goggin, and Ross Fisher saw off Pat Perez.