I think the biggest question is can they actually come up with another good relic/maguffin for Indy to find? The two that always seem to come up the most are Atlantis and Noah's Ark, but frankly they've always sounded pretty lame to me. And they also seem to be lacking the kind of real religious power and significance that the Ark of the Covenant and Holy Grail both had (or heck, even the Sankara Stones with their mysterious dark power).
Or who knows, maybe the best approach is to do what TOD did, and have Indy basically get sucked into an adventure by accident, where he has to rescue a bunch of people or something and the relic is almost incidental to the story.
Or who knows, maybe the best approach is to do what TOD did, and have Indy basically get sucked into an adventure by accident, where he has to rescue a bunch of people or something and the relic is almost incidental to the story.