Unless you're in a hurry or there's no sensible alternative, leave the big highways to the big trucks. If you're headed for a tourist destination during its high season, or your heart's set on a specific hotel or motel, reserve well in advance. That does wonders for peace of mind, particularly if you're not traveling alone. I rarely reserved ahead and never got burned, but my drive was mostly off-season. Better than ever.
New motels seem to be opening daily, particularly along the interstates.
Intense competition is keeping prices down. Chains, for the most part, offer the consistency of a Big Mac. You know what you'll be getting, and that can be nice. The best independents, though, may offer the motel equivalent of great chicken and dumplings. I used both.