Egyptian fans, meanwhile, will hold their breath to see if prolific Liverpool striker Mohamed Salah really has recovered from the shoulder injury he suffered in the Champions League final as the Pharaohs take on Uruguay.
But after host nation Russia's rousing 5-0 win over Saudi Arabia in the tournament opener, the highlight of the day will be Spain's clash with Cristiano Ronaldo's European champions in Sochi.
The Spanish team had been tipped as one of the favourites to win the trophy for a second time after a two-year unbeaten run under Lopetegui.
Real's appointment of Lopetegui could, the federation apparently feared, have opened up Spanish football's age-old faultline between the squad's Madrid and Barcelona-based players.
Ramos, who also skippers Real Madrid, insisted this week's events had not upset any relationships.
"There are no cracks. We are all individuals and we all think differently, but the collective idea is the same -- we are here to go for the World Cup," he said.
Almost 5,000 kilometres away, Lopetegui was being unveiled as the new Madrid coach. The 51-year-old described the day he was sacked as "the saddest day of my life since the death of my mother".
- Blot on Ronaldo's career -
A 19-year-old Ronaldo was playing the last time Portugal beat their Iberian rivals in a major tournament, winning 1-0 to eliminate Spain in the group stage at Euro 2004.
He has gone on to become his country's leading scorer with 81 international goals in 150 appearances.
Yet one doubt hangs over him: his form in a Portugal shirt has never matched his heroics for Manchester United and Real, and his World Cup scoring record so far is poor with just three goals in three tournaments.
Egypt coach Hector Cuper says Salah is "almost 100 percent certain" to start against Uruguay in the Group A match in Ekaterinburg, nearly three weeks since he left the field in Kiev clutching his shoulder in agony after being wrestled to the ground by Ramos.
Friday's other Group B fixture pits Iran, coached by former Real Madrid manager Carlos Queiroz, against Morocco, guided by Frenchman Herve Renard.
"It has been a source of inspiration for us," Queiroz told Sky Sports. He said Nike "should come out and apologise because this arrogant conduct against 23 boys is absolutely ridiculous and unnecessary".
(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)