Spain and the Netherlands maintained their perfect starts to 2012 European Championship qualifying as the continent's heavyweights flexed their muscles on Friday, opening up commanding leads halfway through their group campaigns.
Villa extended his national-record haul to 47 goals with a deflected shot and a penalty in Granada as the Spanish moved six points clear with a fourth straight win.
The Dutch were also playing the closest challenger in their pool but enjoyed a much more comfortable evening, routing Hungary 4-0 for a fifth win in a row in Group E.
Premier League stars Rafael van der Vaart, Dirk Kuyt and Robin van Persie were joined on the scoresheet by Barcelona winger Ibrahim Afellay as free-scoring Netherlands ran riot in Budapest.
Italy and France, two European powers looking to rebuild their reputations after torrid World Cup campaigns in South Africa, also claimed victories on Friday to build healthy cushions in their groups.
The Italians edged past Slovenia 1-0 through a 73rd-minute goal by Brazilian-born midfielder Thiago Motta to go six points clear in Group C.
Roma defender Philippe Mexes and Lyon midfielder Yoann Gourcuff were the scorers for Group D leader France in its routine 2-0 win at last-place Luxembourg. Les Bleus are now four points ahead of second-place Belarus.
Elsewhere, Serbia rallied to beat Northern Ireland 2-1 and Belgium triumphed 2-0 at Austria, with both winners going joint second in Groups C and A respectively.
Germany and Norway, the other two teams to have 100 percent records so far in qualifying, play qualifiers on Saturday.
The Czech Republic threatened an upset by opening the scoring in the 29th minute through Jaroslav Plasil, whose drilled left-foot shot from 25 meters found the corner.
Villa, though, came alive midway through the second half to extend Spain's winning run in competitive games to 10.
He equalized in the 69th with a deflected shot from the edge of the area, having been picked out by Xavi Hernandez, who was making his 100th international appearance. Villa then converted from the spot after Andres Iniesta was fouled by Jan Rezek.
Van der Vaart and Afellay scored first-half goals to put the Netherlands 2-0 ahead by the interval against Hungary.
Van Persie set up Kuyt in the 54th for the third before the Arsenal striker scored himself eight minutes later to complete the rout for the 1988 European champion.
The Dutch are now six points clear of the Hungarians ahead of the reverse fixture between the two countries on Tuesday in Amsterdam.
Motta opened his account for the Azzurri in just his second match for the team, scoring with an angled drive to give the visitors a deserved victory in Slovenia.
Giampaolo Pazzini had earlier hit the post for Italy, which remained unbeaten and has a healthy cushion halfway through its qualifying campaign.
Serbia had no fans to cheer the team on against Northern Ireland as a punishment from UEFA, after a section of the country's supporters rioted during a qualifier against Italy in Genoa in October.
The visitors went ahead when Gareth McAuley looped home a header in the 40th. Some 250 Northern Irish fans celebrated but they were silenced in the second half as goals by Marko Pantelic and Zoran Tosic completed the turnaround by Serbia, which went level on seven points with Slovenia.
Winger Franck Ribery and left back Patrice Evra returned for France after completing bans which stemmed from their key roles in a squad strike during the World Cup.
The fiasco in South Africa seems a distant memory, though, with the French having turned the corner under new coach Laurent Blanc. The win over Luxembourg was their fourth in a row since opening qualifying with a home defeat to Belarus.
Mexes rose highest to head home a free kick by Samir Nasri in the 28th and Gourcuff fired home a low shot in the 72nd.
Standard Liege striker Alex Witsel scored goals either side of halftime to guide Belgium to victory in Vienna, putting his team level with Austria on seven points - five behind Germany.
