The 2004 European champions are 90 minutes from a place at next year's tournament in Brazil after two goals from Konstantinos Mitroglou, either side of a Dimitris Salpingidis strike, put them in control of the two-legged tie.
However, Santos warned there was a long way to go and urged his side not to lose focus ahead of the reverse fixture in Bucharest on Tuesday.
"Nothing is decided yet," he said. "We need to keep a cool head. Everything will be decided Tuesday.
"We have the advantage after the win, but we are only halfway through.
"The players have worked hard and took advantage of the opportunities we had. We hope to do the same during Tuesday's game.
"In the coming days we will be able to release some pressure. Beyond that, we will prepare properly for the next game."
Greece are aiming to qualify for back-to-back World Cup finals for the first time in their history.
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