In February 2010, Ninis made his best appearances with Panathinaikos and generally in his personal career so far in the knockout stage of the UEFA Europa League against AS Roma. That days, Roma was in great form and was second in Serie A. Having played well in the first match, in OAKA, he helped his team win 3–2. However, in Stadio Olimpico in Roma, he did better, than any other time before. He won a penalty, which Djibril Cissé converted to equalizer for Panathinaikos, then the Greek young attacking midfielder scored from 28 meters and in the stoppage time of the first half he made a great pass to Djibril Cissé, who didn't have a problem to score.
On 1 June 2010, Otto Rehhagel named his official 23-man squad for the 2010 FIFA World Cup in South Africa. Ninis made the cut despite limited appearances for Greece. He was used twice, as a substitution in the matches against Nigeria and Argentina. He is also the youngest player to have been selected by Rehhagel, at just 20 years of age.