The Villans succumbed 3-0 at the hands of Chelsea on Saturday at Wembley and they now return to the bread and butter of the Premier League and, with a Europa League place in their sights, three points will be high on their agenda.
However, David Moyes resurgent Merseysiders have found form in recent times and they could move to within a point of their Midlands rivals if they win at Villa Park.
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The Toffees have suffered a solitary loss - at Tottenham Hotspur - in their previous nine league games, winning five and drawing three of the others.
Fine victories over Chelsea, Manchester United and Manchester City in this sequence have significantly aided their challenge and they will be further looking to exploit a Villa side who may be moping after their humbling cup setback.
But Villa's own form is pretty exceptional and they have lost just once in 12 league games, this coming in dramatic fashion as they fell 7-1 at Chelsea.
They have been held to seven draws in this run and their inability to turn these into triumphs has all but ended their top-four challenge this term.
Villa have a full-strength squad to choose from but O'Neill may rest James Milner after he was hurt by England team-mate John Terry that brought the Blues skipper a caution at Wembley.
Mikel Arteta is struggling with a groin complaint but the visitors should be confident that their influential playmaker will make the clash, but long-term injury victims Marouane Fellaini (ankle) and Dan Gosling (cruciate ligament) remain absent.
Last season's clash between the two sides was a cracker at Villa Park and the neutral fan will be hoping for much more of the same this time around.
The contest ended in a 3-3 draw and Everton will look back with regret that they couldn't hold onto a two-goal lead on two occasions.
They stormed into a 2-0 lead thanks to Fellaini and Tim Cahill before the towering John Carew pulled one back on the half hour.