Humphreys is joined at half-back by his promising Ulster team-mate Kieran Campbell in the only other change to the threequarters.
With veteran lock Malcolm O'Kelly ruled out through concussion and rookie Matt McCullough suffering from a dead leg, Leicester's Leo Cullen links up with Donncha O'Callaghan in the second row.
Simon Best features at prop in favour of John Hayes, who is named among the substitutes, while Ulster's Neil Best plugs the gap left by Easterby's demotion from the back row.
Uncapped Munster hooker Jerry Flannery features on an experienced bench which includes Hayes, Mick O'Driscoll, Easterby, Peter Stringer, O'Gara and Girvan Dempsey.
O'Sullivan was expected to make more changes for the easiest match in his side's autumn schedule but the Ireland boss revealed he wanted to take another look at certain combinations.
He said: "We hoped to give some guys a go who weren't involved over the last two games but injuries limited that. We wanted to get some new players on the pitch.
"I wanted to look again at the way Andrew Trimble and Gordon D'Arcy played together because they looked very good as a partnership against Australia.
"The back row have also been playing very well. Denis Leamy has been the success of the autumn internationals and his chemistry with Johnny O'Connor is good. We're trying to build for the Six Nations."
Romania arrived at Lansdowne Road on the back of their first ever victory over Canada after completing a last-gasp 22-20 triumph in Bucharest last Saturday.
They have access to their professionals based in the French league but are still not expected to trouble Ireland who should complete their autumn series on a high.
Ireland team to face Romania at Lansdowne Road on Saturday (1230):
G Murphy (Leicester), S Horgan (Leinster), A Trimble (Ulster), G D'Arcy (Leinster), T Bowe (Ulster), D Humphreys (Ulster), K Campbell (Ulster), M Horan (Munster), S Byrne (Saracens), S Best (Ulster), D O'Callaghan (Munster), L Cullen (Leicester), N Best (Ulster), J O'Connor (Wasps), D Leamy (Munster).
Replacements: J Flannery (Munster), J Hayes (Munster), M O'Driscoll (Munster), S Easterby (Llanelli), P Stringer (Munster), R O'Gara (Munster), G Dempsey (Leinster).