Racism rows cloud standout FA Cup clashes
The lunchtime kick-off at Anfield is the standout tie of the weekend although this time not all the talk has been about football owing to the animosity surrounding Liverpool striker Luis Suarez's eight-match ban for racially abusing United's French left-back Patrice Evra in a Premier League game.
United supporters will travel in their thousands to the home of their arch north-west rivals and while Suarez will not be playing, tensions are expected to run high.
The same can be said of the other Saturday lunchtime kick-off at Loftus Road where Queens Park Rangers host their West London rivals Chelsea - a tie that brings QPR defender Anton Ferdinand into direct contact with John Terry for the first time since he accused the England skipper of racially abusing him.
Terry, who will appear in court next week to answer police charges of racist language towards the brother of England defender Rio, will play, according to Chelsea boss Andre Villas-Boas, and both clubs issued a statement this week attempting to smooth the waters before the derby.
Camera lenses will be trained on Terry and Ferdinand for the obligatory pre-match handshakes, while extra police and stewards have been employed for the game.
Other ties involving Premier League rivals include Everton against Fulham on Friday and Arsenal's home tie against Aston Villa on Sunday.
Meanwhile, those seeking a shock will be keeping an eye on Championship Brighton's home tie against top-flight Newcastle United and high-flying Tottenham Hotspur's short journey to Championship side Watford on Friday.
League Two Crawley Town are the lowest-ranked survivors and will travel to Hull City confident of reaching the fifth round.
The focus will be on Anfield on Saturday, though, when Liverpool face United hoping for only a fourth victory against them in the FA Cup - the most recent coming in the fifth round in 2006 when a Peter Crouch goal earned them a 1-0 win.
United gained revenge for that two seasons ago when Ryan Giggs scored the only goal in a third-round clash in which Liverpool skipper Steven Gerrard was sent off.
Liverpool, criticised by manager Kenny Dalglish for a listless league defeat by Bolton Wanderers last week, responded in fine style on Wednesday by beating Manchester City 3-2 on aggregate to reach the League Cup final, where they will play Championship side Cardiff City.
The 2-2 draw against City would have given Liverpool a huge boost as they prepare to take on United.
"We've got to Wembley. That's all we've achieved so far. We've not been there for a while, so I think that in itself is an achievement - but that's not where our ambitions stop," Dalglish said.
"We want to continue and do as well as we can between now and the end of the season. We'll enjoy the moment tonight for a wee while and then get ourselves concentrated on a difficult game on Saturday."
While rarely free-flowing encounters, United manager Sir Alex Ferguson hopes that the only talking points will be on the pitch.
The Scot stood steadfastly behind Evra and said Suarez's long ban was the "right one" after it was announced but he hopes both clubs will now move on.
He even went as far as writing a letter to fans with tickets, and while not specifically talking about the Evra/Suarez incident, he implored them to support the side in a "positive, witty and loud" way.
Despite being well-placed in the Premier League, Ferguson's side ditched out of the Champions League at the group stage and were humbled by Crystal Palace in the League Cup so Liverpool will face a United team at full tilt on Saturday.
With some tough league fixtures coming up as they attempt to bridge a three-point gap to City, striker Wayne Rooney said beating Liverpool would be the perfect way to launch their charge towards the title.
"They are all difficult games but as a footballer, these are the games you want to play in," Rooney told the club's official website.
"As a player you relish this part of the season and I always feel we're at our best when it gets past new year because we can see the end of the season and that there are trophies to be won."