The Hornets were in control by half-time courtesy of two composed finishes from Matej Vydra, both set up by excellent passes by Almen Abdi.
But Forest's task was made even harder when Ayala, who was booked earlier, picked up his second yellow in the 38th minute. O'Driscoll was trying to bring on Greg Halford but "couldn't get him on quick enough."
He said: "I don't know what it was before half-time, not long, but suck it and see.
"That would have been preferable rather than getting him geared up but you think when you're on a yellow card and the referee's warned you that one more misdemeanour and you're off, you would be a little bit more cautious but Daniel's 20 years of age.
"We've all been young once and made mistakes and unfortunately he's made his."
The visitors had an early chance to take the lead when Andy Reid swung in a dangerous free-kick but Danny Collins glanced his header just wide.
O'Drsiscoll said: "I thought we were a threat. I thought we had the best chance. Danny Collins' header should really have scored, a free header inside the six-yard box.
"The first goal in the Championship is always crucial. They got it, we've been down before but we felt we were still well in the contest.
"But the sending off and probably more crucially, conceding a goal before half-time, once it's 2-0 and your down to 10 men makes it extremely difficult because if you gamble it could be three or four."