Their superiority will be hammered home if they win at home to Norwich and local rivals and reigning champions Manchester United fail to pick up any points on their trip to Aston Villa.
With 11 wins and two draws from their opening 13 league matches, City -- who beat Arsenal in the quarter-finals of the League Cup in midweek -- have hardly put a foot wrong in domestic action all season.
Not that City are taking anything for granted, starting with wealthy owner Sheikh Mansour, the Abu Dhabi-based businessman who has invested some £1 billion into the north-west club.
"We must be aware that these kinds of results can be a double-edged sword -- it makes the others look at you differently and prepare themselves the best way they can," Sheikh Mansour told the Al Ittihad newspaper.
"But those who want to win championships and trophies have to adapt to that and be ready to face the challenges."
Although City have so far endured a faltering Champions League campaign, which could see them fail to qualify for the knockout stages, Mansour said domestic success was his priority this season.
"We must not forget that our main objective is to win the English Premier League and if we achieve that, then it will have an impact on the team and the club as a whole and will show we can achieve anything."
United will try to recover from seeing a second string-side get knocked out of the League Cup by Championship club Crystal Palace when they travel to Villa Park.
Sir Alex Ferguson came as close as he ever does to criticising his players by insisting their midweek display was "not a Manchester United performance" and someone who will be especially keen to make a mark on Saturday is defender Ashley Young, a £16 million pre-season capture from Villa.
Under-pressure Chelsea manager Andre Villas-Boas takes the misfiring Blues to fourth-placed Newcastle insisting he won't abandon the brand of football that helped him guide Porto to a trophy treble last season.
"The philosophy is not a cancer," said Villas-Boas, whose side suffered a second defeat by Liverpool this season, in the League Cup, in midweek.
Also facing an unwelcome spotlight is Chelsea and England captain John Terry, with prosecutors considering whether to press charges against the defender over allegations he racially abused QPR's Anton Ferdinand in a recent west London derby.
Third-placed Tottenham, seven points behind City heading into the weekend and still not out of the title race, will look to continue their impressive start to the season at home to Bolton.
Spurs striker Jermain Defoe insisted talk of a first English title heading to Tottenham in some 50 years was not a fanciful dream.
"Can we win the title? The manager (Harry Redknapp) thinks we can. That's great and I can't see why not."
Meanwhile, bottom of the table Blackburn are at home to Swansea while QPR take on West Brom and Arsenal travel to Wigan.
Sunday sees Sunderland, in their first match since sacking manager Steve Bruce, travel to fellow strugglers Wolves, with Everton facing Stoke.
Liverpool, now without injured Brazil midfielder Lucas Leiva for the rest of the season, are away to Fulham on Monday.
Fixtures (1500GMT unless stated)
Saturday: Aston Villa v Manchester United (1730GMT), Blackburn v Swansea, Manchester City v Norwich, Newcastle v Chelsea (1245GMT), QPR v West Brom, Tottenham v Bolton, Wigan v Arsenal
Sunday: Everton v Stoke, Wolves v Sunderland (1600GMT)
Monday: Fulham v Liverpool (2000GMT)