I sold one of my bikes to a hefty guy and he ran it through every bump and pot hole he could find it seemed. The frame broke right where the seat post runs through the two smaller curved tubes (cruiser style frame). If you use a diamond type frame, you will have more resistance to breaking.
I am a little over 300 and I have a 48cc that hauls me just fine. It is a little sluggish off of the line but with minimal pedal assist I can top most hills at 20mph. Make sure that your pedal side is geared high for pedal asst., too low and you can't keep the bike up to speed and it will stall. My most recent build has a 48t rear sprocket and it does seem to work better on the low end and I'm not losing as much high end as with the 50t...Kelly