Depends on how they do it.

Lara Croft already did Excalibur in TR: Legend. Not sure about the fountain, although Jack Sparrow is on his way there so Drake better hurry.

Your keys though... What legend surrounds them?

Deserts can look cool and not bland. And they could tweak their snow engine to make a sand engine.
Also there are plenty of underground temple possibilities, and more zombie nazis! xD

edit: more

I don't know...I think it's better if they leave out religion. It's pretty cool how Naughty Dog spin history, but religion? That would definitely light some sparks...

Long ago, in the ancient city of Sylvania, a man owned a Mitsubishi Galant.  His house keys, P.O. Box keys, and keys to his mother's (the giver of life) house were on that key ring.  One day, the keys vanished without a trace.  His mother no longer trusted him with keys to her house due to his absent mindedness.  The Mitsubishi no longer exists.  But, to this day, that man would like to go to his mother's house and sleep on her sofa and eat her delcious groceries when she's not home.

And, do you know who that man was?  That man was me. 

Meh, i dunno.

They probably wouldn't have to spin anything. Look at Indie + Last Crusade, they got away with it

So as not to draw too much comparison to Indiana Jones, and still keep the desert theme (and hopefully not offend anyone's religion) Drake could search for the Spear of Destiny?

Good idea. The SoD is what they stabbed Jesus with... Am i right?

Don't the Americans have that? After they took it from Hitler?

Edit: "During the Anschluss, when Austria was annexed to Germany, Adolf Hitler took the lance. It was returned to Austria by American General George S. Patton after World War II and was temporarily stored in the Kunsthistorisches Museum. Currently the Spear is held in the Schatzkammer (Imperial treasury)."

From Wiki :)

If we do (I didn't really do any research.  I just searched my mind for artifacts), we don't deserve it.  Drake needs to steal it and take it on some kind of pilgrimage.