Mixing substrates is not a good idea, for the very reason you mention. Gravity and water movement (water must move through the substrate, and if the tank is biologically balanced it will) will eventually have the sand on the bottom and the gravel on the top.
To the depth, less is better than more. I would not go over 3-4 inches at the deepest point, namely in back areas where plants with extensive root systems like the larger swords would be. Down to 1 inch along the front is fine. As the substrate will shift to even out (same reasons as above), terraces made from rock or perhaps wood will be needed to keep the differing levels.
Anaerobic areas are actually wanted, they are part of the complete biological balance of a n aquarium; but we don't want them taking over the substrate. Plant roots do a lot to prevent this, as do the Malaysian Livebearing snails. [In marine systems there are types of worms that work the same.] There is a bit more info on this aspect here: http://www.tropicalfishkeeping.com/f...quarium-74891/
I now have playsand in 4 tanks, the largest is my 5-foot 115g. The total overall depth was about 2 inches, and I pushed some areas deeper with flat basalt rock for the larger swords, though in the past several months it has, as I mentioned above, evened out a bit. But the plants are established so they manage. I don't touch the substrate, by which I mean no vacuuming, poking, etc. The plants and snails take care of this. Some anaerobic areas do exist, but I've never had hydrogen sulfide problems. I recently did some re-arranging in my 33g that has been setup with sand for over a year, and even in there with 1.5 inches sand I didn't detect issues. Some pretty black areas, but the fish weren't bothered.