Forum consensus will have him stopping at Onslaught (depending on which incarnation of Onslaught it is). Alpha Flight apathy will largely get him past Talisman if they see him getting past Onslaught. And almost all will have him losing to (classic) Strange.
Scoob's right, Nate would put up a good fight. Same with Cable. Chuck would get slaughtered because Despero can block himself telepathically (and possibly just overwhelm Chuck with tp) but then he'd just walk up to him and pull his head off.
I have no opinion personally, but that's what to expect.