Leaders Juventus were held to a 1-1 draw by lowly Genoa in Serie A while in England, Premier League sides Liverpool, Tottenham Hotspur, Aston Villa, Norwich City and Queens Park Rangers were unexpectedly dumped out of the FA Cup in the fourth round.
Lionel Messi hit four goals for leaders Barcelona and Cristiano Ronaldo grabbed a hat-trick for Real Madrid as the arch rivals warmed up for their midweek King's Cup semi-final clash with crushing La Liga victories on Sunday.
Messi took his league tally in 21 games this season to an incredible 33 in Barca's 5-1 win at home to 10-man Osasuna while Ronaldo passed 300 club goals and now has 21 this term as Real thumped Getafe 4-0 at the Bernabeu.
Barca's return to winning ways after last weekend's 3-2 reverse at Real Sociedad, their first defeat of the campaign, put them 11 points clear of second-placed Atletico Madrid, who lost 3-0 at Athletic Bilbao in Sunday's late kickoff.
Champions Real, whose hopes of a second consecutive title are effectively over with 21 of 38 matches played, are four points behind Atletico in third and 15 adrift of Barca, who have taken 58 of 63 points available this season.
Leaders Juventus were held to a 1-1 draw against Genoa after Marco Borriello struck in the 68th minute for the lowly visitors to cancel out Fabio Quagliarella's goal nine minutes after halftime.
Napoli took advantage by winning 2-1 at Parma to end the only unbeaten home record in the league and move into second place, cutting Juve's lead to three points.
Serie A topscorer Edinson Cavani notched an 84th minute winner for Napoli, who have 46 points from 22 games, with his 18th goal of the season.
Lazio dropped to third, a further three points behind, after a shock 1-0 home defeat by Chievo while teenager Mauro Icardi scored four goals as Sampdoria routed troubled Pescara 6-0.
Third-tier Oldham Athletic stunned seven-times winners Liverpool 3-2 on Sunday to cap a weekend of FA Cup fourth-round shocks.
Tottenham Hotspur became another major top-flight casualty after losing 2-1 at Championship (second division) Leeds United, who must now travel to 2011 winners Manchester City.
Holders Chelsea were also heading for a surprise defeat at third-tier Brentford until much-maligned striker Fernando Torres hit a late equaliser to salvage a 2-2 draw and a replay at Stamford Bridge.
Defeat for last season's beaten finalists Liverpool and Spurs took the number of Premier League casualties losing to lower division opponents in the last 32 to five following defeats for Norwich City, Queens Park Rangers and Aston Villa.
Norwich suffered the humiliation of becoming the first top-flight side to lose to a minor league team for 24 years when they were beaten 1-0 at home by Luton Town on Saturday.
Mario Mandzukic scored one goal and created the other as Bundesliga leaders Bayern Munich pulled 11 points clear of their nearest title rivals with a 2-0 victory at VfB Stuttgart on Sunday.
It was a subdued performance by the Bavarians but goals from Mandzukic, after a bad backpass from Cristian Molinaro in the 50th minute, and Thomas Mueller were enough for their 15th win in 19 league games, taking them up to 48 points.
Stuttgart had Martin Harnik sent off 10 minutes from time with a second booking.
Second-placed Bayer Leverkusen are on 37, after a goalless draw at Freiburg on Saturday while champions Borussia Dortmund, closed in on 36 after beating Nuremberg 3-0 on Friday with two goals from Jakub Blaszczykowski.
Paris St Germain were fortunate to claim a 1-0 home win against Lille as they stayed on top of the Ligue 1 on Sunday.
The capital side, who have 45 points from 22 games, prevailed thanks to Aurelien Chedjou's second-half own goal as Lille were denied an obvious goal before the break and hit the woodwork in the closing stages.
Olympique Lyon, who beat Valenciennes 2-0 away, are second on goal difference with Olympique Marseille in third place three points off the pace after a 2-2 draw at Stade Rennes.
Rennes are fourth on 36 points and lead Girondins Bordeaux by one point after the Aquitaine side claimed a 1-0 win at sixth-placed Nice.
Basement side Nancy and second from bottom Troyes eased their relegation fears thanks to 2-1 home wins against Lorient and Stade Brest respectively.
Benfica climbed to the top of the Portuguese Premier League following a 2-1 win at third-placed Braga, turning the championship to virtually a two-horse race.
The Lisbon club's win opened up a three-point lead over Porto, who host Gil Vicente on Monday, while Braga trail the pace setters by 13 points.