The two Manchester clubs take centre stage on Saturday when City host Arsenal and United travel to Tottenham Hotspur for the evening kick-off.
City manager Mark Hughes will welcome the arrival of the Gunners to Eastlands, as the match provides the sternest of tests for his new-look squad after their bright opening to the campaign.
Arsenal were unlucky to leave Old Trafford without at least a point in their last game before the international break and will be out to confirm their status as title contenders against one of the pretenders for a top-four spot.
And if that was not enough motivation for Arsene Wenger's side, the Citizens bought two of their top talents in the summer to add even more spice to the match.
Kolo Toure and Emmanuel Adebayor made the move north in the transfer window and will keen to put one over their former club.
Meanwhile in the 5.15pm kick-off, Tottenham's emergence as a threat to the top four will be assessed further this weekend as the champions arrive at White Hart Lane.
Can Manchester City get the better of Arsenal on Saturday? - Latest Football Betting
United have overcome last month's blip when they surprisingly lost to Burnley and have won their three other games.
However, Spurs are level on points with Chelsea at the top of the table following their 100 per cent start to the campaign, but interestingly they have failed to beat the Old Trafford giants since the last century.
Since that 3-1 victory in 1999, Tottenham have failed to record a win in all competitions against United in 22 meetings, a statistic which will have to be ended quickly if Spurs are to stay in and around the big boys.
Elsewhere in the Premier League, Liverpool entertain Burnley as they look to bounce back from a below-par start to the season which has seen them lose two of their four opening games.
Sportsbook title favourites Chelsea are expected to comfortably roll over Stoke City at the Britannia Stadium and maintain their own blemish-free start to the campaign.
More difficult matches to call are Blackburn Rovers versus Wolves at Ewood Park, Bolton Wanderers' trip to Portsmouth and Sunderland's game at home to Hull City.
From that trio of fixtures, Bolton and Pompey already looks like being a relegation six-pointer as the two teams are struggling in the fledgling table having picked up no points from their opening games.
Saturday's final match sees Wigan Athletic entertain West Ham United with the home side looking to snap a run of three successive defeats.
Their opening day victory over Aston Villa seems like a long time ago and the Latics will be hoping to arrest their slump before a drama escalates into a crisis.