But Sam Allardyce's side overcame their numerical disadvantage to reduce the arrears through Nikola Kalinic after a Guzan error before Carew settled the issue with a late penalty.
Villa boss Martin O'Neill and Allardyce made it clear their priorities lie with Tuesday's Carling Cup semi-final first leg between the clubs by making seven and nine changes respectively.
But Villa's line-up still looked considerably stronger with the likes of Ashley Young, Emile Heskey, James Collins and Habib Beye amongst the players recalled to the starting line-up.
Ashley Young caused constant problems for the visitors and set up both of Villa's goals while youngster Fabian Delph impressed before having to be substituted at half-time through injury.
But Rovers posed more of a threat after the introduction of Morten Gamst Pedersen.
Villa dominated the early stages and forced two corners in quick succession - and, from the second of them, they created the first decent opportunity of the game.
Ashley Young's inswinging centre was met by Delfouneso but he failed to obtain a clean contact on his close range header and Rovers keeper Jason Brown was able to collect.
The pressure from Villa was constant and central defender James Collins had a goal-bound header blocked from yet another Ashley Young corner.
It came as no surprise when Villa broke the deadlock after 12 minutes through Delfouneso's first goal of the campaign.
Delph found Ashley Young on the left flank and he cut inside before sending over a teasing cross which Delfouneso was first to react to and he glanced his header past Brown from 10 yards out.
Ashley Young squandered a golden chance to double Villa's lead after 21 minutes.
Villa's stand-in skipper Nigel Reo-Coker found the England winger in space with a perfectly weighted pass with only Brown to beat.
But the former Watford player was hesitant and allowed Brown the time to spread himself and make the save.
Blackburn had the opportunity to draw level after 31 minutes when Reo-Coker was adjudged to have brought down Steven Reid inside the Villa penalty area.
But Guzan guessed correctly and saved the spot-kick from former Birmingham midfielder Dunn away to his left.
It followed on from his five penalty saves, including four in the shoot-out, against Sunderland in the Carling Cup earlier in the season.
This was to prove a costly lapse for Rovers as after 37 minutes Cuellar doubled Villa's lead.
Michel Salgado was yellow-carded for a challenge on Stephen Warnock and the resulting inswinging free-kick from Ashley Young was met by Cuellar who glanced his header past Brown into the corner of the net.
Blackburn's misery was compounded in the 42nd minute when Diouf was given a straight red card by referee Howard Webb for a lunging touch-line challenge on Beye.
Villa were forced into a half-time substitution with Delph, who had picked up a knock, replaced by Steve Sidwell.
Ashley Young continued to pose problems and a fine pass freed Heskey who took the ball wide of the keeper but was unable to apply the finishing touch.
Rovers made their first change after 53 minutes with Dunn replaced by Zurab Khizanishvili. Then out of the blue an error by Guzan handed Blackburn a life-line 60 seconds later.
The Villa keeper failed to hold onto an inswinging corner from substitute Pedersen and Kalinic had the simple task of tapping the ball into an empty net.
Villa suddenly looked shaky and Kalinic could have levelled matters after being sent clear by Pedersen but he drilled his low shot just past the far post.
Cuellar headed over from a Warnock centre and Brown turned aside a fierce Reo-Coker drive as Villa ended with a flourish.
In the 90th minute Gael Givet brought down Carew in the box and the Norwegian international sent Brown the wrong way from the spot.