Manuel Pellegrini's free-scoring side were taken to a replay by Championship outfit Blackburn Rovers in the last round, but City's incredible home record gives the Hornets little chance of doing the same.
Only Bayern Munich have come away from the Etihad Stadium without tasting defeat during a season in which the League Cup finalists have scored at least three goals in 13 of 17 matches on their own turf.
A run of 18 unbeaten matches for the hosts does nothing to improve Watford's chances, although Pellegrini is likely to leave out several star names ahead of the trip to Tottenham Hotspur on Wednesday.
Others who have been in the treatment room with him recently - Stevan Jovetic and Jack Rodwell - are also in contention to feature, but Samir Nasri remains a long-term absentee with knee ligament damage.
Almen Abdi is on standby to replace Iriney in midfield if the Brazilian is unfit after limping off in the 1-1 draw with Bournemouth, while Sean Murray could line up alongside him if Sannino feels that he needs to sacrifice a striker, possibly Diego Fabbrini, to reinforce the centre of the park.
Possible starting lineups
City: Pantilimon; Richards, Nastasic, Lescott, Kolorov; Milner, Garcia, Rodwell, Navas; Aguero, Dzeko
Watford: Almunia; Doyley, Ekstrand, Hall, Faraoni; Battocchio, McGugan, Murray, Abdi, Pudil; Deeney
Sports Mole says: 4-0