I like how the only main considerations for a hard subject are the core sciences.
I did maths, further maths, physics and chemistry but drama and theatre studies was by far the most challenging. Of course, it's all subjective, so for me the sciences came naturally without an awful lot of effort, but it was the art which required me to really push myself to do well in.
Surely what makes a subject difficult is ultimately its position as being outside your comfort zone? (For the most part, of course; I'm not going to attempt to equate further maths with general studies...)