The Villans go into the weekend 15 points from safety with as many left to play for this season, while United will look to get their top-four push back on track.
While their season doesn't compare to the misery Aston Villa fans have had to endure over the last seven months, United have also suffered a hugely disappointing campaign in 2015-16.
Expected to push on from their return to the top four last season, they once again find themselves embroiled in a battle just to make the Champions League - a battle they look like losing.
Four points is the gap to local rivals Manchester City in the final top-four spot after United's slip-up against Tottenham Hotspur last weekend, when they conceded three goals in the space of six second-half minutes to fall to their first defeat at White Hart Lane since 2001.
It was a sign of both how far Spurs have come and United have fallen in recent seasons, yet against all the odds and despite persistent reports suggesting otherwise, Louis van Gaal remains in the job at Old Trafford.
Whether that would be the case if they do miss out on Champions League football remains to be seen, but with many fans desperate to see Jose Mourinho appointed this summer, any decision to keep the Dutchman would not prove to be a popular one.
The result was their only defeat in their last six games, but they did return to form on Wednesday night to book their place in the semi-finals of the FA Cup at West Ham United's expense.
Another goal from Marcus Rashford, in addition to a Marouane Fellaini strike and more heroics from David de Gea, saw Man Utd win 2-1 in the last ever FA Cup game at the Boleyn Ground, setting up a Wembley showdown with Everton next weekend as they look to win the trophy for the first time since 2004.
Silverware and a top-four finish would certainly represent a good rescue job from United, and they will expect to take a step towards the latter this weekend having won their last four home league games, keeping three clean sheets in the process.
Indeed, United have kept 10 clean sheets from their 15 Premier League outings at Old Trafford this season, boasting the best home defensive record in the division having conceded only seven goals.
Recent form: WWLWWL
Recent form (all competitions): DDWWLW
Saturday looks set to be the date that confirms what has been expected for a long time - Aston Villa will be relegated from the Premier League for the first time ever.
Their fate is not yet mathematically sealed, but realistically they are already dead and buried, with 15 points left to play for this season and 15 points also the gap to Norwich City in 17th.
Villa's dreadful goal difference means that the gap is effectively 16 points, and they could even be relegated before they kick off on Saturday should Norwich avoid defeat in the early match against Sunderland at Carrow Road.
It is hard to argue against this Villa outfit deserving their place amongst the Premier League's worst ever teams, having scored fewer and conceded more than anyone else in the league and won just three times all season.
Only two sides have ever managed fewer than their current tally of 16 points, which hasn't been added to since February 6, with Villa losing eight matches in a row since then, scoring just three goals and conceding 24 in the process.
It is a sorry state of affairs for a club that has won seven league titles, seven FA Cups, five League Cups and the European Cup during their history, and whoever takes on the manager's post this summer will have a huge rebuilding job on his hands.
Nigel Pearson is the new favourite to come in as Remi Garde's permanent successor, while David Moyes's name has also been mentioned as he looks to rebuild his own reputation in this country after his doomed spell at Villa's hosts this weekend.
Planning has already started for life in the Championship, though, and it is hard to see any circumstance where the inevitable will not happen this weekend. Villa have not won any of their last 17 away games in all competitions since the very first day of the season and have scored just five goals in their last 12 league games on the road.
Old Trafford is perhaps the worst place for Villa to visit in such circumstances considering their dreadful record against United, although on current form not many would back Villa to win at any ground in the division.
Last weekend saw them beaten 2-1 at home by Bournemouth in what Cherries boss Eddie Howe described as a "toxic" atmosphere, and it is unlikely to get any better for caretaker boss Eric Black as he goes down with the sinking ship.
Recent form: LLLLLL
United skipper Wayne Rooney came off the bench for the closing minutes in the midweek win over West Ham having missed two months with a knee injury, and he could be restored to the starting XI this weekend.
Rooney has scored 13 Premier League goals against Aston Villa in his career, but he faces a battle to be named up front considering the form of Rashford, who has netted six times in 11 appearances since breaking into the first team.
Fellaini joined Rashford on the scoresheet at Upton Park and he is another who has enjoyed himself against Villa, hitting more goals against them (four) than he has any other Premier League team.
Man Utd possible starting lineup:
De Gea; Fosu-Mensah, Smalling, Blind, Rojo; Schneiderlin, Carrick, Mata, Rooney, Martial; Rashford
Aston Villa possible starting lineup:
Guzan; Bacuna, Lescott, Clark, Cissokho; Sinclair, Sanchez, Gueye, Westwood, Richardson; Ayew
Head To Head
Manchester United have completely dominated this fixture in the Premier League era, losing just one of their last 40 meetings with Villa in the top flight (W29 D10).
The Red Devils are unbeaten in the last 13 meetings in all competitions since Agbonlahor scored the only goal of the game in a 1-0 Villa win at Old Trafford in December 2009.
The reverse fixture this season also saw an away 1-0 win as Januzaj struck in a rare Friday night game back in August to give United two wins from two at the start of the season.
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We say: Man Utd 3-0 Aston Villa
It is hard to see anything other than a comfortable home win in this match. United have had their problems this season, but they have been good at home recently and are facing a side who gave up all hope of survival some time ago. The Red Devils also need a win to keep their Champions League dreams alive, so it would be a major shock if they were to do anything but cruise to victory.