I am also a biggie. @5'10" 301#(down from 424):thumbup: I have found most bikes that I've tried pretty willing to hold me up. I think something with at least a seat-post shock will make his ride more comfortable. I started riding 2 mos ago on a $98 Roadmaster mountain bike w/ all rigid frame. I quickly learned that I needed to upgrade. I looked at a few comfort hybrids by Raleigh and Cannondale, but I found I was uncomfortable with the upright position since I was already getting used to the mtn bike. I ended up with a used Specialized road bike that I love so far. The skinny wheels seem to hold me just fine.
Best advice, take him to a few shops to ride a few different bikes to get a feel for what he'll be comfortable on. Don't worry so much about his size.
ChipR