Breath of Fire: Drahon Quarter is definitely a franchise killer - and I say that as someone who adores the game and actually probably considers it the pinnacle of said series. I feel that, especially in very niche franchises with a specific, rigid identity (which BoF definitely was), any deviation of the norm will be met with fan scrutiny in various degrees. Even Breath of Fire IV, despite being an excellent game with really sophisticated storytelling for a PS1 JRPG, was already shat upon by the fanbase because of its change in tone and setting. Then Dragon Quarter came around with an extremely experimental... well everything, and while many modern gamers come into it now and really appreciate its ambition and how ahead of its time it was, back then it just alienated people who wanted an epic medieval fantasy with dragons even further.
The same goes for Silent Hill 4. Another game that I hold in really high regard and is my second favorite right after 2, but was still hated enough by the fans (again, essentially for being different - though of course the game has its share of flaws) that that was pretty much the end of Japan-made Silent Hill, not to mention the interest in later titles was much poorer. It may not have killed its franchise as hard as DQ, but it definitely put it in a severe coma. Maybe it’s for the better, considering what happened with the brand after
As a bit of a side note, Yahtzee sums up my thoughts on the game pretty well in a recent video and I’m so happy I’m not alone!