Except for one being realtime 3D and the other one prerendered?
The story I guess.
I'm not sure but I think Uru takes place in the present while the Myst games take place a long time ago.
In the Myst games it is Atrus that has taken the task upon himself to restore the D'ni empire, while in Uru you see a modern cooperation is trying to restore D'ni (D'ni Restoration Council) and, while Myst gives a rather idealized view of the D'ni civilization... Uru shows the player the true D'ni empire and its (not so pretty) history (slavery, immense greed...)
The Myst games don't really handle the D'ni empire itself, mostly Atrus and his family.
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pat b
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