Gods, there's millions of them. Although I suppose the majority are exceedingly obscure. A few of the large scale questions I would pose are:
Why do we have such exceedingly capable brains?
How does consciousness work, and why did it evolve?
Why haven't plants closed the green gap?
Why hasn't a version of Rubisco without the oxidase activity evolved?
What, exactly, is the evolutionary relationship of viruses to the rest of life and to each other?
What is the nature of the link between Archaea and Eukarya?
Why do Archaea have such different membrane lipids to the other two domains of life?
How significant has horizontal gene transfer been in the evolution of higher organisms? Especially in the light of the evidence that the mammalian placenta relies on a gene jobbed from a retrovirus.
How did life get started anyway?