I find that trying to target highbies systemically just results in lowbie deaths. Highbies get that way because they play smart, not because the system can't kill them.
This is quite true. Often when Highbies (what I would define as characters with 305 or more build, though really is chapter-dependent) die, it is because they
choose to stay in a situation - or get into a situation - where they KNOW they will get killed on purpose.
To use a fairly recent example: the previous campaign in Seattle (valley of ghosts) was pretty rough, especially the BBG fights, but the ones who 99.99% of the time ended up res'ing? Lowbies and mid-level characters (which is nobody's fault, that is just how things played out) because the highbies were really cautious (especially vs the Tree and LoE).
In my mind, you want more "highbie" deaths, give them a reason to want to die - a cause, a friend, a noble, a house, etc. - tell stories that make them want to choose to make that sacrifice. The ever-present question: "Is this worth dying for?" Make that answer "Yes." and you'll see more risks, and perhaps, more deaths.
Further, you pretty much have to break the system and steam roll them anyway to make a death stick.
I don't know about "breaking" the system being the only way; certainly over-stat'ing or over-using auto-res mechanics (I'm amazed more of those don't stick) are ways to res a character, but *I* wouldn't call those game-breaking though others could feel differently.
For what it's worth, the last two plot teams in Seattle have over-stat'd monsters and cards (as every Plot team does sometimes...scaling is an art, not a science), but they have ALSO made (and keep making), concerted efforts to bring those cards down to a more reasonable level. They try (and tried) to make things challenging, but I don't think there has been a directed effort to kill highbies (or anyone). But that has been my experience and is my viewpoint, others may feel differently.