The pair, who proved so destructive in black and white shirts as the Magpies fought their way back into the Barclays Premier League, are now back in harness at West Ham, who visit St James' Park on Sunday.
They will need no introduction to the current crop of Newcastle players, and full-back Santon knows stopping them could prove the key to the home side's chances of extending their five-game unbeaten run in all competitions.
The 21-year-old Italian said: "West Ham will be a difficult game. They have some good players.
"They have Andy Carroll and Kevin Nolan, so we have to be careful.
"It is very important for us to win the game. We are only playing for a win.
"We have to stop them. We know they are coming here to score. However, we know we have a great defence here. We have a great team and we can stop them."
Carroll and Nolan both left the club in controversial circumstances, the former in exchange for a staggering £35million from Liverpool and the latter after his hopes of securing a new long-term deal were dashed.
But while midfielder Nolan has gone from strength to strength at Upton Park, where he arrived in June last year, Carroll has joined him by a circuitous route.
The 23-year-old found himself surplus to requirements at Anfield in the wake of new manager Brendan Rodgers' appointment and, having been linked with a move back to Newcastle, eventually joined the Hammers on loan for the season in August.
But while both played key roles during their time on Tyneside, Alan Pardew's men have gone from strength to strength since their respective departures and finished fifth in the league last season to earn a return to European football.
Indeed, they very nearly gatecrashed the top four and the race for Champions League qualification, and that remains an ambition.
Santon said: "Last year, we had a really big chance to get there.
"We finished fifth in the end, but we have a very good team and have a good chance of getting there.
"We just have to get back into the winning mentality every game.
"We are in a great position to move forward."
Newcastle are yet to produce their best form on a consistent basis so far this season, but are unbeaten since they lost 3-0 at home to Manchester United on October 7.
They extended that run in Belgium on Thursday evening when, after carelessly conceding twice to Club Brugge within the opening 19 minutes, they fought back to claim a draw which edged them closer to the knockout stage of the Europa League.
Santon said: "I think it was better that neither ourselves nor Brugge won the other night. It is better for our mentality.
"We can still get through in Europe, but we are now ready to win tomorrow [Sunday].
"This game is very important. We have a lot of confidence and we can win. Now we have to focus on the Premier League again."
However, Pardew will be without key men Fabricio Coloccini and Cheick Tiote through suspension, while full-back Danny Simpson remains a doubt with a shoulder problem.
Mike Williamson, who was withdrawn early from the 2-2 draw at the Jan Breydel Stadion, will start alongside Steven Taylor, who replaced him, in central defence, while Jonas Gutierrez, Hatem Ben Arfa and Demba Ba are likely to return.