There's a HUGEGANTIC thread on this very topic over in the Hi-Po Shop right now that has some VERY good info in it from the guys who have actually done the swap (or are in the process of doing it) and lived to tell about it.
Also:
I've seen an S10 with a 350 shoehorned into the engine cavity before. There isn't a whole lot of extra room, but it works without too much modification, as the S10 frame was originally designed to accomdate an SBC (IINM).
Most of the guys who do the S10 frame swap go to V-8 engines, it seems, but an I6 would be cool to see mounted in there.
