It depends on the remainder of your trip, but if one didn't care whether they ended up at Cantwell vs. Paxson, I'd also suggest east - west. You'd end up in Cantwell, see some spectacular scenery on the way there, and have a few more miles of similar scenery driving on North to Healy or Squarebanks.
On the other hand, if you're like me and always trying (with diminishing returns) to find the Old Alaska on the road system, going west to east puts you in the more-like-old-Alaska area of Paxson with access to Tok, Nabesna, etc, etc, etc.