I didn't see it mentioned (maybe it was, I admittedly only sort of skimmed) but in regards to screwing yourself by despawning enemies and not having enough souls... there are a couple areas in the game where there are infinite enemies. One section has two areas (one right next to a bonfire which makes it convenient) that have mechanics where they realize if you despawned everything and managed to not do a thing correctly you would be locked out of continuing. So the enemies infinite spawn. Technically there is a third area in this same section but once you do the thing the guys stop coming at that location. They aren't worth a ton of souls but often if I found myself not too far from a level up or the amount I needed to buy something I would go farm that room for a little bit (with some gear I had on me that gave bonus souls I got 444 per guy, 6 guys in the room, I could 1 hit kill each of them, turn around hit the bonfire and do it again all in less than a minute).
Then elsewhere in the game there is a section where some very low value guys will infinite spawn while other more valuable guys spawn due to certain actions. In one of these areas you can pull out a bow and use 2 to 3 arrows per guy (4 guys spawn for about 800 souls each) and then the game will actually respawn them for you while you stand there infinitely... if you do it right. Otherwise you might have to do it a little more manually but still, no bonfire required.
Long story short, if you don't mess with summoning/being summoned which is it's own ample supply of souls it would still basically be impossible to completely screw yourself. You just might make it harder and more time consuming.