Scholars and critics alike agree that the "overwhelming question" that is the focus of all of Prufrock's ponderings in the poem is most likely a marriage proposal, or a question of a woman's feelings for him. He obviously cares for a woman, is intimidated by her, has spent time with her, and wants to speak his heart to her. He either wants to propose and get an answer, or to reveal his love for her and have her reveal how she feels for him. If anyone has been in a situation where they care deeply for someone but are unsure of that person's feelings for them, they can relate to his paranoia, obsession and fears in regards to the subject.
The poem opens up with a reference to Dante's Inferno; it speaks of a man asking for forgiveness before he commits the crime that he has in mind. This can be tied to Prufrock's question, because he wants to be able to guess the woman's answer before he ever asks the question. He doesn't want to ask the question unless he can be reassured of her positive response; if he asks, and gets a negative response, it will be too devestating for him to handle. He wouldn't recover. Just as Dante's lines states "since no one has ever returned alive from this depth," Prufrock fears that he won't ever be able to return alive after receiving a negative answer from her. He fears her answer; the entire poem is him trying to get up the courage to ask her, but he fears that once he has "disturbed the universe" she will just, as he puts in the poem, sigh, and say, "That is not what I meant at all/that is not it, at all," referring to his supposition that she cared for him.
In the end, he decides it's not worth asking. It's not worth risking a no from her, a rejection of him. He chickens out, and resolves himself to the fact that he is a bit of a coward, and that he will forever be one of those people who looks on and longs from afar, but never partakes of the joys that he craves. I hope that those thoughts helped a bit; good luck!