I might go to Fairbanks, but down the Richardson highway rather than going all the way to Tok. Route 2 to Tok, and the Tok cut-off, are not exceptionally scenic--though far from ugly. Tok is mostly a supply and small commercial center, not particularly a destination in its own right.
If you go to Fairbanks, the UAF LARS (Large Animal Research Station) is well worth a stop and the (inexpensive) tour. You get nice and close to muskoxen and caribou/reindeer, and at least when I was there a very informative presentation on those animals...almost too informative, really.
Route 2 is kept open year round. You shouldn't have any problems there, though I suppose a freak blizzard is not technically impossible (but would not stick around too long). A fair number of the touristy things will be closed or closing that time of year (no matter where you go). Reservations for campgrounds other than Denali Tek (or perhaps other Denali campgrounds) should not be necessary in the slightest.