Everton fans will be proud to call their fifth-placed side "big" as they again push for the top four despite modest means compared to United and second-placed champions Manchester City.
However, apart from August's aberration, United's record is so good against those in the upper echelons of the Premier League that Everton might have more of a chance by reverting to their old role as underdogs bravely battling for a famous scalp.
"[In the league] you hope that the return we've had from the big games is going to be significant. We've won at Liverpool, Chelsea, Manchester City and we were 30 seconds away from a really good result at Tottenham," United boss Ferguson told the club's official Inside United magazine.
"All in all we've had a good return from these kinds of games and hopefully they will prove significant at the end of the season."
David Moyes' Everton sit three points behind Tottenham, who occupy the fourth and final Champions League spot, after a solid season marked by the mercurial midfield talents and goals of Marouane Fellaini.
The Belgian scored the only goal in the season-opening win over United at Goodison Park and was again instrumental in last weekend's 3-3 draw at home to Aston Villa when he scored twice, including heading in an injury-time equaliser.
He will be the dangerman United's sometimes shaky defence will be keeping their eyes on but Ferguson believes all his top names will now be up for the fight in the title run-in.
"You hope that the players realise that the league is there for them [to win]," Ferguson said.
"It's obviously a big challenge and we've got the FA Cup and the Champions League as well, and managing the squad is going to be important when it comes to picking the right teams. That's down to myself and the staff.
"We've got players back from injury, which is important, and I usually find that during the second half of the season when the big games come along everyone is fit."
City can put some pressure on United if they win at Southampton on Saturday as they try to produce a similar comeback to last season when they beat United to the title having been eight points behind with six games left.
Roberto Mancini's side have 13 games to claw back nine points this time and after last weekend's 2-2 draw with Liverpool, the Italian said he was confident in his side.
"There have been plenty of times in the past when gaps like this have been made up," he said. "Our target is to get into the Manchester derby in April just two or three points behind."
History shows Mancini is right with last season's fightback not the only time a big lead has been whittled away late on.
United were eight behind with 10 games left in 2003 but overhauled Arsenal.
Roles were reversed in 1998 with Arsenal 12 points off United with 13 games to go before the Londone
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