What happened to Yennefer?
Yennefer's journey in the first season builds toward a final display of devastating magical power in the last moments of "Much More," the series finale. She rains magical fire upon the attacking Nilfgaardian force and then… disappears. Her mage allies look for her but don't find her afterward. We don't yet know the nature of the power she let loose or if/how she'll return, but we do know she's a major character throughout the series, and killing her off at the end of Season 1 seems silly. Yennefer will be back, somehow.
Who wins this war and how will it affect these characters?
Relatedly, we need to know the immediate political outcome of the Battle of Sodden Hill. Hopefully this is where Season 2 picks up, showing us what the redrawn map looks like after a massive magically and conventionally fought battle at a strategically important Nilfgaard stronghold. With Princess Ciri on the run, Yennefer missing, and the mage Vilgefortz embedding a mace in his former ally's head in the last episode, there's no way Geralt won't be caught in the middle of it all. And if Ciri somehow makes it out the conflict alive, she will have to reckon with her destiny as the Lion Cub of Cintra. Will she have to rule? Will she be married off? Will she fight, the way her grandmother did? We'll see.
How do Ciri's powers work?
This is an even bigger question for Ciri. This is a world where humans are both suspicious and fearful of magic but also seek to manipulate it like any other tool or weapon. The in-universe compendium book of lore written by Marcin Batylda, The World of the Witcher, describes it as "Art, Chaos, and Science: a blessing, a curse, and progress." Those conflicting definitions and the groups that have stakes in them will play into how Ciri continues to use and learn about her newfound powers moving forward, and it'll be interesting to see how the show handles them.
Which stories will be adapted next?
The Witcher Season 1 adapted tales from the Sapkowski's short story collections The Last Wish and Sword of Destiny, and its plot runs the three central characters chronologically up to where we meet them in Blood of Elves, the first novel in Sapkowski's saga. The question is how closely the show will follow Blood of Elves, and whether we'll see it intercut with more of Sapkowski's short stories or even flash-forward to the events we see in the video games (which take place years after the books end). Hissrich has said that she has seven seasons plotted out with the intention of following the books throughout, much like HBO's Game of Thrones followed George R.R. Martin's books, but that could be a misdirect, and plenty of writing can change between seasons.