In Italy, 19-year-old Argentine Mauro Icardi scored twice as
leaders Juventus suffered a shock 2-1 home defeat by lowly Sampdoria and Liverpool's Luis Suarez was again the villain of the piece in the FA Cup third round.
The Uruguayan striker appeared to handle before scoring to help Liverpool avoid embarrassment and edge to a nervy 2-1 win over minor league Mansfield Town.
Olympique Lyon became the first French Cup holders to be eliminated in the round of 64 in 15 years, suffering a shock loss on penalties to third division Epinal.
Leaders Barcelona moved 11 points clear at the top of La Liga with a 4-0 rout of city rivals Espanyol as second-placed Atletico Madrid drew 1-1 at Real Mallorca.
With coach Tito Vilanova back in the dugout at the Nou Camp after his throat operation, Pedro scored twice and Xavi and world player of the year Lionel Messi bagged one apiece, the latter notching his 27th league goal of the campaign.
Second-placed Atletico Madrid missed suspended top scorer Radamel Falcao in a 1-1 draw at Real Mallorca in which Kevin Garcia grabbed a late equaliser for the hosts after Raul Garcia had put the visitors in front.
Real were five points further back in third after surviving a sixth-minute red card for reserve keeper Antonio Adan, chosen ahead of Iker Casillas again, with a 4-3 win over Real Sociedad at the Bernabeu.
Xabi Prieto netted a hat-trick for the visitors but Karim Benzema, Sami Khedira and a second-half double from Cristiano Ronaldo secured the points and eased the pressure on coach Jose Mourinho after three games without a win in all competitions.
Manchester United striker Robin van Persie showed his brilliance once again as he came off the bench to finish clinically and rescue a 2-2 draw against West Ham United in the FA Cup third round.
New signing Demba Ba scored twice on his debut as Chelsea routed fellow Premier League club Southampton 5-1 and Tottenham Hotspur eased past 1987 Cup final opponents Coventry City 3-0 thanks to two goals from Clint Dempsey.
Liverpool beat minor league opponents Mansfield Town 2-1 on Sunday with a controversial second goal from Luis Suarez who clearly handled before smashing home.
There were three goals in the final nine minutes as Arsenal and Swansea City drew 2-2 in another all-Premier League clash.
Leaders Juventus suffered a shock 2-1 loss at home to lowly Sampdoria despite taking a 24th-minute lead through a Sebastian Giovinco penalty.
Sampdoria had Gaetano Berardi sent off in the 31st minute but won thanks to two second-half goals from Argentine 19-year-old Mauro Icardi.
Juve's lead was cut to five points over Lazio, who beat Cagliari 2-1, as the 38-match Serie A campaign reached the halfway mark.
Uruguay forward Edinson Cavani scored a hat-trick to lead Napoli to a 4-1 win over AS Roma which took them into third place ahead of Fiorentina and Inter Milan who both lost.
Olympique Lyon became the first French Cup holders to be eliminated in the round of 64 in 15 years when they suffered a shock loss on penalties at third division Epinal after a thrilling 3-3 draw.
Four other Ligue 1 teams lost to lower division sides, with fourth-tier Plabennec grabbing the headlines by dumping out Stade Reims 1-0 while Ajaccio, Stade Rennes and Bastia were also defeated.
Ligue 1 leaders Paris St Germain won 4-3 at fifth-division amateurs Arras and will face Toulouse in the stand-out tie of the draw for the last 32.
Andre-Pierre Gignac scored twice to help Olympique Marseille labour to a 2-1 home win over second tier Guingamp.
Champions Porto and fierce rivals Benfica both won to keep the two-horse race going at the top of the Portuguese Premier League with Porto three points behind the Lisbon club with a game in hand before the pair clash in Lisbon next Sunday.
Colombia striker Jackson Martinez headed in Porto's winner from a corner as the hosts scraped a 1-0 win over Madeira island side Nacional despite a lacklustre performance.
Benfica eased past Estoril 3-1 away with Argentine winger Nicolas Gaitan opening the scoring with a neat backheel and setting up another. The Lisbon club are on 35 points after 13 matches with Porto on 32 from 12. (Editing by Toby Davis and Ed Osmond)