Bondo doesn't really have any reinforcement, which is why you shouldn't use it very thick. Plus, it's talc based and will absorb water. If you really have to fill up the whole channel, and don't want to do it the long way, use fiberglass reinforced bondo, the green/blue stuff. It's stronger and won't absorb water. Sand down to bare metal, and leave a nice coarse finish to the metal for some tooth...
There really isn't a good way to do this with body filler, because whatever you do it will make a heavy chunk of plastic that will eventually fall off or crack or whatever. There really isn't a lot of surface area to bond to relative to the weight of body filler, so a nice piece of fiberglass cloth that lays over the filled channel and overlaps the doorskin a bit might help. Reinforcement is key..
If you just want to cover the square holes, a few layers of fiberglass laid all along the molding channel will be plenty strong and keep the thickness even.

Oh yeah, the best way to do it if you want to fill the whole channel is to get a body shop to cut a strip of metal to cover the channel, basically the same technique as shaving door handles, etc..