I can't believe I haven't said anything here yet.
Well, we've had the Ark of the Covenant in Raiders, the Sankara Stones in Temple, the Holy Grail in Crusade, and the Skull of Akator (also, dispelling the myth of El Dorado) in Kingdom.
That still leaves a veritable wealth of mythology for Lucas to mine from. I doubt he'll dip into the same mythology twice, so I'd steer clear from anything in Jewish, Christian, or Hindu mythology now. That means great relics like the Staff of Aaron or the Spear of Destiny probably won't appear.
Things like Sun-Wu Kung's Garden of Immortal Peaches, the Fountain of Youth, artefacts involving eternal life, seem unlikely also - remember, the plotline concerning eternal youth and life was done with the Grail in Crusade, so it's unlikely to be visited again. So those few are out.
The Golden Fleece and Noah's Ark are nice choices, admittedly. But how would they work as MacGuffins, exactly? Noah's Ark has no purpose except for sitting atop Mount Ararat like a rotting boat which, technically, it is. And the Golden Fleece, in mythology, holds no actual power - it's just golden and shiny. So, nice as they are, these two are also unlikely.
Relics like Excalibur, Mjolnir, or the lost city of Atlantis, are popular choices, and probably work well in a fifth Indiana Jones movie. They've got my top votes, personally - each stays away from mythologies already explored, and are sufficiently different to the aforementioned quartet of relics Indy's already found.
But in terms of a MacGuffin, I believe - for the fifth film - it should work like Last Crusade: instead of having the film be all about that MacGuffin, it should be a secondary relic to the more important figure that Indy must find. In this case, I'd make it Abner Ravenwood. Have Indy find Abner Ravenwood, and learn his disappearance ties into the Nazis living in South America, who want Excalibur/Mjolnir/Atlantis. Go from there!!
And that's my semi-researched input.