This match is always going to be a huge deal, one of the marquee fixtures in the Premier League.
Both managers rested top players for their midweek European engagements in preparation for this match, but the gamble paid off for Roy Hodgson a lot more than it did for Alex Ferguson.
However, looking at their last domestic fixtures, United did almost everything right for 90 minutes before Everton made their heroic comeback, whereas Liverpool were lucky to leave Birmingham with a point.
No Liverpool manager in the Premier League era has ever won their first match against Manchester United, and I don't think Hodgson will break that trend.
At the moment, he doesn't seem to know what his best team is, and he hasn't been allowed to make as many changes as he would have liked. They still suffer from the same lack of creativity that was the undoing of Rafael Benitez.
Fernando Torres was left out of the win over Steaua Bucharest, but I believe that was to do with revitalising him mentally rather than physically. Hodgson offered his support after the striker drew criticism from many - including myself - for his lacklustre performance at St Andrew's, saying that he needed to gain match fitness.
But is he going to do that from the stands while his team-mates are playing second-rate opposition? That's just the sort of game Torres needed to get under his belt.
Of course, Torres has a great record against United, and with their defence looking as uncertain as it is at the moment, he may well extend that.
A lot of expectation has been placed upon Rio Ferdinand's imminent return as the answer to their problems at the back, but the England captain has missed a lot of football. It will take him a while to get back to anywhere near the player he was, if he ever does at all. When you get to a certain age it becomes harder to recuperate, and I don't think that the Ferdinand-Vidic partnership will ever get back to the strength it was when they were last champions.
Not only that, but right-back is also an area with little stability in the United squad, with no one to bridge the gap between Gary Neville's experience and Rafael da Silva's youthful exuberance.
The most fascinating aspect of the latest instalment of this huge grudge match is that neither side is anywhere near its best, which will make victory all the more sweet for the winner.
Since arriving for such a huge fee from Spain in the summer, Silva has had little time to settle at his new club in between jetting off to Mexico, Liechtenstein and most recently Argentina for internationals.
Now, however, he has a decent run of club games ahead of him in which to finally show if he can adapt to the English game. He won't be given the same amount of time and space as he did in La Liga, so it will be interesting to see how he copes with that.
Of course, he opened his account for City in Europe this week, but he is well used to playing in European competition from his time at Valencia.
Roberto Mancini was singing his praises after the win in Salzburg and, from his perspective, if you want a new signing to hit the ground running then a match against Wigan should be ideal.
If Silva can get a full 90 minutes under his belt at the DW Stadium and retain his place for the trip to West Brom then he may give Chelsea something extra to think about when they visit Eastlands next weekend.
Under pressure: David Moyes (Everton v Newcastle United)
Following their late rescue act against United last week, expectations will be high among Everton fans that their customary bad start to the season is over.
They usually manage to raise their game for the big matches, but the true test of whether they are on an upward trajectory will come in a fixture such as the visit of Newcastle. The Magpies have already shown themselves to be no slouches, but they are still a side Toffees fans would expect to get three points from at home.
If they fail to get their first win on the board five matches into the season, then they really are facing the prospect of having to drag themselves up the table.
Upset of the weekend: Tottenham Hotspur v Wolverhampton Wanderers
Spurs' defeat at home to Wigan the weekend after they sealed their place in the Champions League was quickly put down to a European hangover. I'd be more inclined to call it a Big Time Charlie hangover.
They were riding on the crest of a wave, thinking they had made it to the top table, and they took their eyes off the ball. Harry Redknapp has to make sure that his players don't make the same mistake again and remind them that while they eventually came back from Bremen with a point, they did so because they blew a two-goal lead. They are by no means the real deal yet.
The arrival of Wolves, who did the double over them last season, will provide a real test of just how much character Tottenham have as a group.
Mick McCarthy looks to have built a side that could be in the Premier League for a while yet. He has made them very hard to beat, and they are capable of the odd surprise result.
Wolves may be a rough and physical team, but the biggest obstacle between Spurs and three points on Saturday is their own mentality going into the match. It doesn't matter how dirty Wolves play - as long as Tottenham play to their potential then they should win. Whether they will or not is another question.
- Roy Hodgson
- Fernando Torres