Hwy 340 out bkk is probably the most pleasant. Hwy 1 up to Ayuthaya is pretty awful. Though between Ayuthaya and Lopburi not so bad. Busy around Nakhon Sawan.
I'll often break up the trip and stay a night or two in Kamphaeng Phet. There are some nice cheap hotels along the river. Very pleasant area with good food and a very interesting historical park.
Just west of Tak is a lovely waterfall. Makes for a pleasant break, it's short hike and beautifull cool water. By time you get up there ya really appreciate the cool. If you aren't in a hurry stop for a night or two in Lampang. There's a great backpacker guest house right on the river run by an interesting Thai guy who into 4x4's and bikes. There's great massage school for a real Thai massage. The evening scene in the center of town is pretty cool.
In Kamphaeng Phet is also a nice guest house called the 3J guest house. The owner speaks great english and also hss resort up in the mountains nearby. It's really pretty country around there. Worth hanging out a couple days. Hardly any tourists go there.
If you're really not in a hurry run the Mae Hong Song loop from the south and stay in Mae Sariang.