Dear god that terrible.
Yes, that can happen, and whenever it happens thats a failed run. That would mess even a Transmuter up, and transmuter's actually good for VGT. I've been saying that VGT is too random for a while now - if I didn't have thousands of gold to spare I wouldn't even be attempting it. I doesn't have to be this random, especialy if a VT run of it is supposed to be doable.
On the other hand, if they make it fixed (made more static) in some way, we'd find a solution, an optimal sequence and beat it with everything. I don't think it's doable if one of the big exploration floors turns up fully revealed, especaily now that the undead are bloodless. The no-xp floor is also very problematic wherever it happens. There's other small things that can mess you up as well. I don't know how to give feedback on it, I don't know what was intended, so I don't know what to do about it.
But it seems to me that the one thing that makes it much harder than the previous incarnations, regardless of "rocks fall everyone dies" mechanisms, is that you can't plan ahead very well. If we could somehow know the sequence of altars that we get in a run, or the sequence of challenges (by having statues of whatever next to the stairs or the spot where stairs spawn), even if we could only see the one after the current one, I think it would be easier.
EDIT: In the sense that when considering a strat or play sequence that's "viable" in VGT, right now, is pretty inflexible. You always have to be ready for just about every nasty hazard at once, and you only find out what's your next objective or what's your next got when you're done with the current one. And every floor can contain challenges for every type of character at the same time, so you have to be ready for everything all the time which means focusing on cheeze-or-bust. Having any idea about when to save an inventory slot, when to convert something, or pick up a situational item for the next floor at least, or to look for alternative solutions while you get to the res stacking gods would be huge.
People would probably use this to scum, but scumming in VGT is an expensive sport, and I'm not sure I would've even attempted scumming for GETINDARE if I wasn't playing the guy who starts with LEMISI.