Sandwiched in between those tussles, Arsenal will be looking to reclaim top spot, for a few hours at least, when they host Crystal Palace as part of a Super Sunday double-header that will also see Liverpool attempt to keep themselves in the hunt for the top-flight crown away at West Bromwich Albion.
Elsewhere, the current occupants of the bottom three places in the division - West Ham United, Cardiff City and Fulham - will all be hoping to enjoy home comforts when they face Swansea City, Norwich City and Southampton respectively.
Everton will want to put midweek derby disappointment behind them when they return to Goodison Park against Aston Villa, while fellow top-four chasers Manchester United and Tottenham Hotspur will be looking to ensure that Stoke City and Hull City remain stuck in a rut.
Newcastle United suffered an agonising 2-1 reversal against north east foes Sunderland at the Stadium of Light earlier in the season and have now gone four derby dates without success. Alan Pardew will be hoping that trend can be bucked on Saturday lunchtime as the Magpies welcome the Black Cats to St James' Park. Sunderland will make the short trip to Tyneside buoyed by a recent upturn in fortune which has lifted them out of the relegation zone and to within six points of the top half. Newcastle, meanwhile, will be hoping that new frontman Luuk de Jong can hit the ground running and help to cover the loss of influential midfielder Yohan Cabaye to Paris St Germain.
Any slip-up from Gus Poyet's men would open the door to those below them, with the battle to avoid the drop growing ever tighter. West Ham United are two points adrift of safety at present, but will have taken considerable heart from a battling 0-0 draw at capital rivals Chelsea on Wednesday. Jose Mourinho accused the Hammers of playing 'football from the 19th century' at Stamford Bridge, but Sam Allardyce has laughed off the criticism and would settle for more of the same if it guarantees a positive result at home to Swansea City - with a whole host of fresh faces poised to make their Upton Park bows on Saturday.
Cardiff City continue to prop up the division and Ole Gunnar Solskjaer's managerial credentials will be tested to the full from this point on. The Norwegian is still looking for his first Premier League point as a manager, with the Bluebirds having lost four on the spin and gone seven games without success in top-flight competition. They have, however, collected 12 of their 18 points so far in front of their own supporters and will be calling on the south Wales natives to get behind them once again when they entertain Norwich City - a side who have been struggling to get anything going themselves of late.
Perched just above Cardiff are Fulham, with Rene Meulensteen having been unable to turn the tide at Craven Cottage following his appointment as successor to Martin Jol. Three straight defeats have kept the capital outfit in trouble and the leakiest defence in the top flight has now been breached on 50 occasions. Plugging those holes is a must, and the fightback needs to start against Southampton. The Saints will be in no mood to offer up any favours, though, as they look to nail down a top-half standing. They are unbeaten in their last three in the league and, according to their boss Mauricio Pochettino, put in a 'sensational' performance during a 2-2 draw with Arsenal last time out.
Away from the bottom, Everton head into the weekend licking the wounds inflicted by Liverpool in a 4-0 Merseyside derby humbling at Anfield on Tuesday. Roberto Martinez has not seen his troops drop their guard quite so dramatically this season as they did on the other side of Stanley Park, and he will be calling for an immediate response. Victory over Aston Villa on Saturday would keep the Toffees very much in top-four contention, with it possible that they could return to the UEFA Champions League places if results go their way. Villa, who sit tenth, have gone seven games at Goodison without defeat, though, and will be riding the crest of a wave after experiencing contrasting fortunes against local rivals in the week - with Paul Lambert's men having edged a seven-goal thriller with West Brom.
Tottenham Hotspur were also involved in a high-scoring fixture on Wednesday, but found themselves on the wrong end of a 5-1 thumping by Manchester City. Being reduced to 10 men did Spurs few favours at White Hart Lane and they will hope that keeping 11 on the field at Hull City produces a different outcome. They would appear to be running into the Tigers at a good time, with Steve Bruce's side having slipped down the standings on the back of four defeats on the bounce. Just four points now separate Hull from the drop zone and they need big-money signings Shane Long and Nikica Jelavic to start offering a return on the investment made in them if a basement battle is to be avoided.
Should Spurs come unstuck again on Saturday afternoon, they could end the weekend level on points with Manchester United. For all of their struggles this season, the Red Devils are just six points adrift of the top four and know that they still have a few gears to go through if everything clicks into place. Juan Mata has been drafted in to help provide that spark, and he made a winning start to his Old Trafford career in midweek. Robin van Persie and Wayne Rooney also came back into the reckoning against Cardiff on Tuesday and David Moyes suddenly finds himself in the enviable position of being able to unleash a wealth of attacking talent on Premier League opponents. Stoke City will be all too aware of that fact as they prepare to welcome United to the Britannia Stadium in the midst of a six-match winless run which has dropped them into trouble.
While much of the attention on Saturday will be directed at events towards the bottom of the Premier League standings, focus shifts swiftly to the tussle at the top on Sunday. Liverpool, fresh from their demolition job of Everton, remain in the running for the title even if a top-four finish is considered to be the sole target for those at Anfield. With those above them not in action until after their encounter with West Bromwich Albion has finished, the Reds could leave The Hawthorns just four points behind the leaders. The Baggies will want to put a serious dent in those ambitions, but they remain without a win under new boss Pepe Mel and will be charged with the task of trying to contain the free-scoring Daniel Sturridge and Luis Suarez in front of the Sky Sports cameras.
The second instalment of a Super Sunday double-header will be beamed live from Emirates Stadium, as Arsenal look to make their way back to the summit. The Gunners were knocked from their lofty perch in midweek, but will return to pole position with victory over Crystal Palace. Despite a 2-2 draw with Southampton on Tuesday seeing Arsene Wenger's men drop points for the first time in six outings, questions have been raised as to their title 'bottle'. There would be no better way to respond to those critics than by sweeping aside London rivals who, despite still looking anxiously over their shoulder, have come into form and pulled four points clear of the top-flight trapdoor - with Tony Pulis' arrival at Selhurst Park having had the desired effect.
Wenger, Pulis and the rest of the sporting world will then settle down for Monday Night Football to see how Manchester City and Chelsea fare at the Etihad Stadium. Success for the hosts would see them end the weekend where they start it - at the top of the pile - while an away win would mean two Premier League heavyweights find themselves locked together on 53 points. It promises to be an epic encounter and it will be interesting to see how Manuel Pellegrini and Jose Mourinho tackle the challenge. A 100 per cent record on home soil suggests that City will go for the jugular, with eight straight wins collected in the league and a phenomenal goal return taking them on to 68 in just 23 games. Chelsea, though, boast the best defensive record in the division, have won five of their last six in the league and have at their disposal arguably the most adept coach in the business at winning mental mind games and delivering success.