Manchester City suffered an unceremonious exit from the FA Cup on Sunday, three days before it tries to overturn a 2-0 deficit at Barcelona in the Champions League.
Cristiano Ronaldo, meanwhile, had little trouble guiding his rampant Real Madrid to another win that left it alone at the top of the table in Spain.
Juventus won to continue its march to the Italian title. Borussia Dortmund eked out a victory as it remained in a distant second place behind German leader Bayern Munich, and Lille won to stay in third place in France.
Second-tier Wigan stunned Manchester City for the second straight year in the FA Cup, beating the Premier League giants 2-1 to reach the semifinals and stay on course to retain the trophy.
Seven days after winning the League Cup final at Wembley Stadium, City was looking to return to the ''Home of Football'' for the last four of the FA Cup and avenge last season's surprise defeat to Wigan in the final in May.
However, Jordi Gomez and James Perch put Wigan 2-0 ahead by the 47th minute at Etihad Stadium and managed to hold on after Samir Nasri gave City hope in the 68th.
''People kept saying we were lucky last year,'' Wigan captain Emmerson Boyce said, ''but we're going back to Wembley and we're making history again.''
Wigan's reward is a semifinal against Arsenal, which is now overwhelming favorite for the competition following it 4-1 win over Everton on Saturday and won't have a better opportunity to end its nine-year trophy drought.
Also on Sunday, Sheffield United became the first third-tier team to reach the semifinals since 2001 by beating Charlton 2-0 and will next play Hull, which defeated Sunderland 3-0.
Cristiano Ronaldo helped Real Madrid reclaim sole possession of the Spanish league, scoring one goal and setting up another in a dominant 3-0 victory over 10-man Levante at the Santiago Bernabeu.
Ronaldo recorded his league-leading 24th goal of the season to get Madrid rolling in the 11th.
The Ballon d'Or winner then passed for Marcelo to score in the 49th and ensure Madrid extended its undefeated streak in all competitions to 29 straight matches.
With Madrid firmly in control, the game turned testy with several bookings until David Navarro saw a direct red for tackling Ronaldo from behind in the 64th.
Ronaldo went close to getting another goal when he hit the crossbar after Levante defender Nikos Karabelas had already scored an own goal in the 82nd.
Madrid moved three points clear of Atletico Madrid and four points ahead of Barcelona.
''We have a small advantage in the league but we can't think about anything else other than the next game,'' said Madrid manager Carlo Ancelotti. ''It's risky not to.''
Juventus took a giant step towards a third straight Serie A title after beating Fiorentina 1-0 to extend its lead at the top of the standings to 14 points with second-placed Roma losing 1-0 at Napoli.
Roma has a game in hand but now second place is even at risk for the capital side as Napoli moved to within three points with the win.
Kwadwo Asamoah scored a brilliant goal three minutes from halftime to give Juventus the lead.
''I feel we're 50% champions, there are still 11 matches left,'' Juventus coach Antonio Conte said.
Inter Milan is only a point behind fourth-placed Fiorentina after beating Torino 1-0.
Borussia Dortmund captain Sebastian Kehl scored the only goal as his team consolidated second place in the Bundesliga with a 1-0 win at his former club Freiburg.
Kehl's goal came against the run of play in the 58th when he swept the ball over Freiburg goalkeeper Oliver Baumann from around 25 meters with his left foot.
Dortmund restored its 20-point gap behind runaway leader Bayern Munich.
Center back Marko Basa and striker Nolan Roux scored a goal each as Lille beat Montpellier 2-0 to strengthen its grip on third place in the French league.
The win gives Lille some breathing space as fourth-placed Saint-Etienne fell four points behind, following a 1-0 loss at midtable Lorient.