"What course did you like the least?"
"What course did you struggle in the most?"
This is an easier answer because you don't have to show off your strength here. All you have to do is make sure you don't pick a subject that relates to your job. It is also safer to pick something that most people do not enjoy. Finally, picking something that you are not good at is acceptable if it is not a skill required on the job. My long example will be about a drama class.
Short Answers
"I didn't enjoy history that much. It wasn't that difficult, but it didn't allow me to think creatively. Most of the classes I took were about memorizing dates and facts. So history is my least favorite subject."
"I struggled in a music class the most. I really enjoy listening to music so I tried to learn a little about it. But it was a disaster. My tone was off and I couldn't tell if something was flat or not."
"My least favorite class was probably poetry. During that course I struggled writing a real poem. I realized I am not a poet."
"I disliked my geography class. It wasn't difficult, but I simply didn't find it very interesting."
Long Answer
"For me, I had a tough time in my drama class. I didn't realize that I was a terrible actor. I didn't think it would be that hard, but week after week, my instructor would point out problem after problem. He gave me a B, but I think it was because of my effort, not because of my abilities. I say this because when I saw myself on video, oh my gosh, it was terrible."
You are putting yourself down a lot here, but in this example it is actually good. Interviewers are worried that a person who can act well will be able to lie about many things during the interview. A person without acting skills will not be able to hide automatic body gestures that the interviewer is looking at. Also, this answer is good because it shows that this person never gives up and puts in a lot of effort.