Most of the rust is generated in these areas due to dirt and moisture kicked up by the tires, and the lack of paint or other rust preventative measures. Any welding is going to burn away your paint protection, so I would suggest the following.
Perform necessary repairs to fender outer skin, having fitted the area to the running board for correct contour. Make inner stiffener strip for the hole area and insure it has correct contour to fit snugly inside the fender with no gaps around the perimeter. Media blast all areas, and cover each separately with a couple coats of a good epoxy primer. Let flash well, but while you are still within the recoat window, brush a heavy application of the same epoxy primer on the areas that will be adjacent to each other, and then quickly bolt the stiffener strip inside the fender and let the epoxy cure. Brush around the perimeter after bolting to help with sealing around the perimeter of the strip. With no welding to burn away at the protective coating, this will be about your best bet at future rust prevention in this area..
