The Champions League kicks off this week with four English sides gunning for continental glory once more.
But for the two Manchester giants, there will also be half an eye on the weekend ahead when they meet in the first of two derby encounters this season.
The clash at the Etihad Stadium will dominate the build-up to the weekend's action, but it is not the only standout fixture of a round that offers some intriguing match-ups.
Mark Hughes takes his Stoke side to play Arsenal in North London and will hope to build on an impressive display in holding Manchester City to a 0-0 draw this past week—a game the Potters could easily have won.
On Saturday, two of the league's in-form sides, Liverpool and Southampton, meet at Anfield with visiting manager Mauricio Pochettino no doubt hoping for better luck than his team experienced against West Ham on Sunday.
Had it not been for the excellence of goalkeeper Jussi Jaaskelainen, the Saints would have won comfortably at St Mary's Stadium. Instead, the South Coast outfit had to be content with a 0-0 draw and the knowledge they put in a good performance.
Elsewhere, West Ham vs. Everton and Chelsea vs. Fulham should offer great entertainment on Saturday afternoon.
Liverpool vs. Southampton
Quite how Southampton didn't beat West Ham on Sunday remains a mystery, but they will do well to match that performance on Matchday 5 when a difficult visit to high-flying Liverpool awaits.
Brendan Rodgers' side have been excellent thus far this season and with two home wins already under their belt, the Reds will be hopeful of maintaining their 100 percent record at Anfield.
However, Southampton will be difficult opponents. Pochettino's side are excellent on the ball and average 59.1 percent of possession in their matches this season. That technical craft, though, is combined with a physical edge that also sees the Saints win an impressive 57.4 percent of their aerial battles, per Whoscored.
Given both sides' strong defensive records this campaign, it may not be a high-scoring encounter. It should, though, be a high-quality clash that serves as a good indicator as to which direction both teams are heading this season.
Arsenal vs. Stoke
The speed at which Stoke have altered their tactics away from the long-ball era of former boss Tony Pulis deserves applauding, with Hughes' side now in the league's top 10 in terms of average possession per Whoscored—a vast improvement on last campaign.
When considered that they have already played two of the top six in Liverpool and Man City, games in which they have conceded a total of one goal, it is an impressive start to the new era at the Britannia Stadium.
In Arsenal, though, they will encounter one of the Premier League's form sides of recent weeks, Arsene Wenger's men having recorded five straight victories in all competitions since an opening day defeat to Aston Villa.
Had Theo Walcott been more clinical against Sunderland, they could easily have scored more than the three they eventually managed. Stoke will be tested to the limit by the Gunners' creative players and will be hoping their opponents have a post-Champions League hangover on Sunday.
Man City vs. Man Utd
The undisputed clash of the weekend comes on Sunday afternoon when two of the Premier League title favourites go head-to-head at the Etihad Stadium.
Neither side has been particularly impressive this season, with David Moyes' Manchester United efficient but lacking in style and Manuel Pellegrini's City misfiring since their opening weekend demolition of Newcastle.
It is on occasions like this, though, that both managers will be scrutinised in their every move and derby defeat so early in their new jobs is a prospect both will be desperate to avoid.
Robin van Persie's goals have generally been enough for United this season, but memories of defeat to Liverpool will be fresh in supporters' minds.
For City, Pellegrini must ensure the disappointing showings of the past couple of weeks will not be repeated when the pressure is on.
It is too early in the season to say it is a match that is in any way title-deciding, but whichever team emerges victorious will pick up vital momentum ahead of future challenges.