Michael Owen penalty while Villa had taken the lead at Upton Park through skipper Gareth Barry.
A win to Villa and a loss to Everton would have seen the Villains finish in fifth due to their superior goal difference, but Joleon Lescott eased Everton's fears when he put his side ahead once more.
As thunderclouds gathered overhead on an unseasonably hot Spring day in Liverpool, Yakubu added a third from the spot to secure the win for Everton, while Villa could only draw 2-2 as Dean Ashton scored for West Ham with two minutes remaining.
Blackburn, meanwhile, secured seventh position, despite losing 4-1 to a Birmingham City side which was ultimately relegated to the Championship after finishing 19th.
Both 18th-placed Reading and Birmingham knew they had to win on the last day to have any chance of surviving the drop, but they also had to rely on 17th-placed Fulham either losing or drawing its final match at Portsmouth (eighth).
But, when Danny Murphy nodded home Jimmy Bullard's free kick to give Fulham a 1-0 victory over Portsmouth, both Birmingham and Reading were relegated, despite the Royals producing a 4-0 victory over the dismal Derby (last).
It was a close thing for Fulham, however, as it finished the season on 36 points alongside Reading, but maintained its top-flight status on goal difference.
In the final match of the afternoon, Sven-Goran Eriksson's time at Manchester City (ninth) appears to have come to an end on a sour note as his side was belted from pillar to post in an 8-1 rout by Middlesbrough (13th).
City had skipper Richard Dunne somewhat unfairly dismissed in the 15th minute and it did not recover as Alfonso Alves produced a hat-trick for Boro on the way to its best win in recent times, while Eriksson looks likely to be sacked by City's Thai billionaire president Thaksin Shinawatra.
English Premiership League - Final Round 2007-08
Wigan 0
Manchester United 2 (Ronaldo 33p, Giggs 80)
Manchester United wins English Premiership
Chelsea 1 (Shevchenko 61)
Bolton 1 (Taylor 90)
Birmingham City 4 (Murphy 31, Jerome 73, 89, Muamba 90)
Blackburn 1 (Pedersen 49)
Derby 0
Reading 4 (Harper 15, Kitson 61, Doyle 69, Lita 90)
Portsmouth 0
Fulham 1 (Murphy 76)
Sunderland 0
Arsenal 1 (Walcott 24)
Tottenham 0
Liverpool 2 (Voronin 69, Torres 74)
West Ham 2 (Solano 8, Ashton 88)
Aston Villa 2 (Young 14, Barry 58)
Middlesbrough 8 (Downing 16p, 58, Alves 37, 60, 90, Johnson 70, Rochemback 80, Aliadiere 85)
Manchester City 1 (Elano 87)
Everton 3 (Yakubu 28, 82p, Lescott 70)
Newcastle 1 (Owen 47p)