It has left them with it all to do in front of their own fans at Villa Park on Thursday night - especially as they know that conceding a goal would mean them having to score three to get past the Austrians.
O'Neill said: "Obviously we are at a disadvantage. We will have to go with all guns blazing in the game mindful of the fact that then we might end up having to score three to win.
"It is a game to be careful about but by the same token not to be too cautious.
"Vienna will present difficulties to us. But the confidence we got from the win over Liverpool on Monday will stand us in good stead.
"It could happen that we might well concede an early goal but we have shown in the past that we can come back from a deficit."
Villa's bid to score the goals they need to get past Vienna could be boosted by the return of striker John Carew who has missed the first three games of the season through injury and illness.
Winger Ashley Young also hopes to recover from a knee problem that he suffered during the 3-1 win at Liverpool on Monday.
After such a high-tempo performance at Anfield, O'Neill admits he may have to make changes to his side but accepts that will not be easy.
He added: "We will have another look at the team. It is a difficult balance trying to change the side around without losing cohesion and still trying to win competitive games.
"But there will be one or two after the exertions of Monday night I will have a look to see how they are.
"Ashley Young, for instance, came off at the end. He is still uncomfortable but is feeling better than right after the Liverpool game."
Villa defender Habib Beye thinks that the momentum built up by the success at Anfield could hold the key to seeing off the challenge of Vienna.
Beye, who joined Villa in a £2.5m deal from Newcastle United last month, said: "The way we played at Liverpool we showed our quality and how we can fight with the top four.
"We do need to do it week and week out as it is of no use doing it just for one game.
"It will be a tough game against Vienna because when we played away it was difficult.
"They have a strong team and scored an important early goal which made us chase the game.
"But I feel we have the quality to win the game and progress into the qualifying stage."