Santos recalled experienced striker Fanis Gekas and also included Bologna midfielder Panagiotis Kone, although he must sit out the first match at home due to suspension.
The Greeks had to settle for a play-off spot after finishing behind European qualifying Group G winners Bosnia-Herzegovina only on goal difference, while Romania were a distant second in their group behind the Netherlands and have not qualified for a World Cup finals since 1998.
"There is confidence and faith in the squad. The Romanians have an excellent team but I think in the end we will qualify," the Portuguese Santos said.
Goalkeepers: Michalis Sifakis (Atromitos), Orestis Karnezis (Granada/ESP), Stefanos Kapino (Panathinaikos)
Defenders: Vasilis Torosidis (Roma/ITA), Loukas Vyntra (Levante/ESP), Sokratis Papastathopoulos (Borussia Dortmund/GER), Kostas Manolas, Jose Holebas, Dimitris Siovas (all Olympiakos), Giorgos Tzavellas (PAOK)
Midfielders: Kostas Katsouranis, Alexandros Tziolis (both PAOK), Panayiotis Tachtsidis (Catania/ITA), Panagiotis Kone (Bologna/ITA), Giannis Maniatis, Andreas Samaris (both Olympiakos), Giorgos Karagounis (Fulham/ENG), Sotiris Ninis (PAOK), Kostas Fortounis (FC Kaiserslautern/GER)
Forwards: Kostas Mitroglou (Olympiakos), Fanis Gekas (Konyaspor/TUR), Lazaros Christodoulopoulos (Bologna/ITA), Dimitris Salpingidis (PAOK), Giorgos Samaras (Celtic/SCO)