With "Pirates 4" being the Fountain of Youth, I doubt they'd put Indy in anything that felt like that. Not sure what is exciting about the Garden of Eden exactly. I mean, there's no skull or ark. Indy needs that 'thing'.
After the aliens in this one, it's also gonna be hard to go back to mystical "God" stuff. Figuring out a good premise with a good McGuffin for Indy 5 is a real trick.
Maybe something out of the Da Vinci Code type thing.
I doubt Lucas is really paying attention to Pirates, and I think Indy 5 would come out before a Pirates 4. I just have a feeling that a Pirates 4 isn't going to happen, at least not in the next 5 years. And if there is going to be an Indy 5 those involved know it has to happen soon before Harrison passes the 70 yr mark. But who knows? And they should stay as far away from Da Vinci Code/National Treasure type stuff as they can.
I agree Indy needs some sort of artifact, if only to sell toys and have an 'icon', but discovering a mystical location seems pretty good too whether it be Shangri-la or Atlantis or the Bermuda Triangle - that's even more a part of archeology than grave robbing/treasure hunting. An Indy 5 should stay away from political 1960s stuff IMO and focus on a more distant land regional mysticism hearkening back to TOD. They've done jungle - twice now, Indian temple caves, and a desert - an adventure in snow covered mountains seems like a good new exotic location.