After a disapponting 2-0 defeat to Wigan on the opening day of the season followed by a 1-0 reverse in Vienna on Thursday, the Claret and Blue could really do with a pick-me-up.
But, they face a seemingly monumental challenge as Steven Gerrard and Fernando Torres among others await on Merseyside on Monday night.
The England midfielder has so often been a thorn in the side of Villa and he is unlikely to provide any respite for O'Neill and co tonight.
Of course, former Villan Gareth Barry could have been lining-up alongside Gerrard in the Liverpool midfield had he not valued money over tradition this summer.
That fact wont have escaped Villa's current central department, which could include Stiliyan Petrov and Nigel Reo-Coker as Fabian Delph is likely to be withdrawn from the limelight.
Reo-Coker's presence in the line-up could be key if he is given the chance to prove himself as he possesses the tenacity and tough tackling ability to stifle Gerrard.
If O'Neill once again goes with Delph, he must brace himself for a big backlash from the Villa faithful, who firmly believe the former Leeds whiz kid is not yet ready for such a burden to be placed upon his fragile shoulders.
The Liverpool midfield, like that of their opponents, has a massive void which will need to be filled.
Flair
The absence of Spanish sensation Xabi Alonso could be key as Rafa Benitez looks to live up to expectations and bring the title to Anfield.
Just as Barry ran the show for Villa, Alonso teed up countless opportunities for front runners Gerrard and Torres.
And as much as Gabby Agbonlahor and Ashley Young will miss Barry, the Liverpool strikeforce will feel the lack of flair in their team.
So, could Villa catch their hosts by surprise and cause an early season upset.
Well, the bookies will give you odds of up to 8/1 that they don't, but then again when do O'Neill's side ever relish the tag of favourites.
All of their best work last season came when the least was expected. In games against Arsenal and Everton, Villa pulled a rabbit out of the hat.
Now they have the chance to prove a few critics wrong and it is an opportunity that Emile Heskey and Agbonlahor should relish. If they can't perform on the big stage then they should not be at the club and nights like these sort the men from the boys.
So, stand up Emile, stand up Gabby, this is your chance to really kick-start what could be a cracking campaign should O'Neill make the relevant additions to his promising squad before the transfer deadline.
It won't be easy, but what a boost it would be should Villa snatch victory from the jaws of predicted defeat.
Likely line-up
Friedel
Beye Davies Cuellar Shorey
Milner Reo-Coker Petrov Young
Heskey Agbonlahor