Vrba, who will take charge of the Czech Republic national team from the start of next year, labelled the performance the best of his side's UEFA Champions League campaign.
Plzen were level at 2-2 with 12 minutes remaining at Etihad Stadium before Alvaro Negredo and Edin Dzeko scored for City, who are second in Group D.
Despite their fifth loss in as many group games, which has left them bottom of the table, Vrba was pleased with his side.
"I'm very happy we have been able to build on our success in the Europa League two years ago with a very good performance tonight," the 49-year-old Czech coach said.
"My team were very strong and it was a great performance – I'm only not happy with the final result."
Vrba said the only difference between the teams was their finishing, lamenting his side's failure to add to their two goals.
"We must not forget we were up against an extremely strong team. We played really well and at half-time the stats were level," he said.
"In the second half we got into their box a lot, though (City goalkeeper) Joe Hart had a good game. In the end, they were better at converting their chances.
"I'm pleased we scored two goals away but we could have scored even more."
Vrba's men were beaten 3-0 and 5-0 in their first two matches against City and Bayern respectively.
But their two recent outings against the same teams have resulted in 1-0 and 4-2 defeats, highlighting their improvement.
"Tonight's performance should not be compared with our away game against Bayern (a 5-0 loss), where we played with too much respect and fear and struggled the whole match," Vrba said.
"In contrast, we enjoyed it tonight. Unfortunately we didn't get a point but nevertheless we played football that we do not have to be ashamed of. It was our best display in the group stage."
