Champions and Bosses are a great start, Diet is an easy addition (it does force you to explore more efficiently) and Swarm too, beyond that it depends on your preferred playstyle. As a grass-abuse huntress player, Barren is still off and Darkness was the last I added, but this can change greatly if you use a different approach
In your opinion, which challenges are easiest to get started with?
Most challenges I managed to beat was with three: hostile champions, badder bosses, and swarm intelligence.
Champions and Bosses are a great start, Diet is an easy addition (it does force you to explore more efficiently) and Swarm too, beyond that it depends on your preferred playstyle. As a grass-abuse huntress player, Barren is still off and Darkness was the last I added, but this can change greatly if you use a different approach