I know this is a reallllly long way off but Casey reiterating that the primary mechanic of the game is that players deal with one room at a time got me thinking about a cool boss mechanic.
So for an ultra-powerful boss (maybe end-game boss not sure) I think it would be a cool idea to have this one boss be able to hit the player hard enough that the handmade_hero actually breaks through walls and spills into multiple rooms like so:
______________________________
|Go Back Through, Handmade_Hero|
V
| | |
\ \ \
================================-K
/ / /
| | |
but where the damage remains as a permanent scar on the land.
Considering the name of the game is Handmade Hero, I'd imagine that Casey has a good deal of introspection in mind for the actual story of the game. With this in mind, I think it's a cool idea for two reasons. First, on the shallow understanding of the event, this boss has the power to actually bend the fabric of reality (for the characters in the game) to it's will by actually creating a hole between two separate rooms. This is powerful in and of itself because presumably at this point the player will have a thorough understanding of what to expect in the game and having this as an event will really throw the player off guard (maybe even have the puzzles of the room mix into a super-puzzle with combinatorics, as Casey mentioned would be utilized).
On a deeper understanding of the event, the core mechanic of this boss is literally turning the game from what Casey (and I'm sorry if I'm putting words in his mouth, this is just my impression) may see as a good game in the genre into a bad game. Perverting the handmade hero into being the tool that turns the game world from closed-scope puzzle-adventure, into an open-world hand-holding adventure (note the ASCII message is part of the bosses attack) one attack at a time.
I don't know if I'm completely missing the point here, we were just talking about the core mechanics of the game and I thought it might be fun to find a reason to break them a little :)
EDIT: sorry about the awful ascii picture, its really hard to format it right