For this task I would stick to the character of George Milton. He definitely is the central character that is most affected by the plot--of course, next to Lennie, who dies in the novel. However, George would have answers that Lennie, due to being Lennie and not having learned his reality to the fullest, cannot answer.
Moreover, George undergoes the traumatic event of having to make a terminal decision regarding his friend. That alone should be a source of many interesting questions.
Some questions to ask George would be:
1. How did you meet Lennie?
George and Lennie have been together since childhood. In fact, George remembers Lennie's Aunt Clara with much more clarity than Lennie does himself. (Ch. 1)
2. Why is Lennie always with you?
(As per his conversation with Slim) Lennie and George were both from Auburn. Aunt Clara had known George as a child. She had taken Lennie since he was a baby. Lennie and George grew up together, always with the understanding that George was the leader and Lennie the follower. Lennie always compensated for his lack of interest with physical strength. George knew from the start that Lennie could never make it on his own. The two grew used to one another, perhaps even co-dependent. Their lives were isolated to begin with.
3. Where did you work before Soledad?
A town named Weed.
4. Why did you leave?
Lennie saw a girl in a red dress and was captivated by the thought of touching the soft fabric. He approached her to touch the dress but was too rough and wouldn't let go. The girl cried rape and they had to escape. (Ch. 3)
5. What is it like living with Lennie?
Sometimes George wonders how much easier life would be without Lennie. (Ch. 2)
6. What are your plans in life?
To "live off the fatta the lan" (Ch. 1), George wants to have his own farm and animals to tend. Lennie is also included in his dream.
7. What do you think of Curley? (Ch. 2)
George thinks Curley has a chip on his shoulder, that he is a "little man," and he does not like types like that. He would even let Lennie hit him a few times if ever need be.
8. What made you make the last decision of ending Lennie's life?
Lennie had already offended Curley once when he broke his hand after Curley bothered him. Curley was going to find anything in his power to get revenge. What was coming to Lennie was a lynch mob led by an angry man, not by a grieving husband. Curley could not have cared less that his wife was dead. He would have brutally murdered Lennie and put him through a considerable amount of torture and pain. By ending Lennie's life with a gunshot to the head, George saved Lennie the pain of being tortured.