Man, that's a big one...
With limited access to the underside, you might have a tricky project ahead of you.
My gut feeling would be bevel back the existing edges of the hole, and create a plug of the correct dimensions with a matching bevel, of slightly less thickness so that there's a slight depression in the deck when installed, i.e. the plug will sit even with the original plywood core with a depression at least equal to the thickness of the glass layer on top of the plywood. Grind down the deck around the beveled surface to provide a surface for fiberglass cloth to adhere, 12:1 ratio to the height of the depression to be filled with glass. Wrap the plug in fiberglass and epoxy resin, and wet out the plywood core with epoxy. Glue it into the deck with thickened resin while the epoxy on the core is still tacky. Then lay a few layers of fiberglass mat over the whole surface. Sand down, fair with thickened epoxy or other fairing compound, and re-gelcoat.
Others will probably have a better answer, but that's how I'd approach it. Still a toss-up on how well it will hold up to any flex in the deck with just one side of the plug glassed in.
If you're planning to re-SeaDek the cockpit or put a section over the livewell hole, you may be able to get away with less attention to the final gelcoat finish.
The thru-hull drain, you could do something similar. Grind down both sides 12:1 ratio of the thickness of the outer layer of fiberglass (NOT the transom thickness), cut a dowel section to fit the hole, coat the dowel and exposed plywood core with epoxy, glue it in with thickened epoxy, few layers of glass on each side, sand, fair, and gelcoat.
At any rate, prepare to get dusty and itchy during this one.
