We can assume that someone big will probably die near the end. Any guesses?
It depends on where Jim wants Harry to be at the end of the case books. I've considered the idea that Harry would try to retire, only to get pulled back into things for the BAT. (Personally, I like the idea of Harry deciding to focus on finding new talents and teaching them to avoid making more warlocks; he's mentioned it too many times during the series, and his major orphan complexes would certainly make it appealing to him). For his retirement to make the most sense, I'd say it would be motivated by Harry seeing too many people he cares about dying.
Higher possibilities (in my mind):
Ebenezer. Harry's biggest ally on the White Council, and one of a handful of people Harry actually respects. I don't see Eb lasting through the books.
The Merlin. Mostly because that would mess things up a whole lot. I also really want to see what kind of death curse Arthur Langtry could pull off (Chernobyl 2.0).
Murphy, because Harry needs to suffer. Few things would make him turn his back on the wider world than losing Murphy. I don't want her to die, but I think it's possible.
This might not be popular, but I'd say Will or Georgia. I'm leaning toward Will, because Jim has put Georgia through the ringer enough times (what's the over/under on how many times she'll get kidnapped in Brief Cases?)
Lower possibilities:
Toot-Toot. He was there at the beginning of the case books, and I think his arc will end at the end of them.
Thomas. I think he'll have a role to play in the BAT, so I think it's less likely, but I could see Jim offing him for similar reasons to Murphy. Alternately, Justine, which would put
Thomas through hell, setting him up for his role in the BAT.
Hendricks and Gard. I think Marcone really needs to be in a different place for the BAT, and losing two trusted associates would rattle him like little else.
Beyond these, I have no ideas. There are truly evil things Jim could do to us, but I don't think they'd better serve the narrative than the above.