Costing a reported £17 million from Blackburn Rovers, the South American was City's second major summer signing after Gareth Barry. But after undergoing knee surgery, the Paraguayan's recovery was overshadowed by the arrivals of Carlos Tevez and Emmanuel Adebayor.
Many predicted that Craig Bellamy, who many viewed as City's fifth choice striker behind Robinho, Tevez, Santa Cruz and Adebayor, would also be overshadowed amid all the competition for places, but he has flourished in City's excellent start to the season.
And after Santa Cruz finally made his debut against the Hammers at Eastlands, Hughes insisted the Paraguayan can go on and make a similar impact to Bellamy.
"Certainly there were a few eyebrows raised when I brought Craig to the club,'' recalled Hughes. "People doubted him and his ability. I certainly didn't because I knew what I was getting.
"It will be the same with Roque. I know the talent he has. I know the attributes he has and I know what kind of guy he is. He is a driven guy. He is ambitious and he wants to win. The challenge is there, not just for him and Craig, but everybody in the squad.''
The Paraguayan struggled with injury in his final months at Blackburn and those problems resurfaced in the early days of pre-season training at City, with Santa Cruz often thinking about playing through the pain.
"I always try to push things,'' he said. "Sometimes the physios have to stop you doing silly things. You always want to be on the pitch playing, no matter how painful it is, especially having come to a new club. In that sense it has been very helpful to have people around. You need to listen and not rush things.''
And Santa Cruz, who scored 23 goals in 57 appearances for Blackburn before his move to Eastlands, revealed that he has been desperate to return to first-team action.
"It has been frustrating,'' he said. "It is hard for a player not to be involved when the season starts, especially when you are new into the club. At the same time I have been very pleased watching the players perform. I think we deserve to be where we are in the table because of the hard work we have been doing and the fantastic way we have started the season.''