The rule that resolves most of this: book what is genuinely scarce, and leave open what is not.
Scarcity is the whole criterion, and it varies enormously by destination and season rather than by how organised you are.
Book in advance:
- Flights, obviously
- Anything with limited daily capacity - a permit, a timed entry, a popular restaurant, a specific tour
- Long-distance trains where reservations sell out or the price rises steeply
- Accommodation in a place with genuinely little of it - small islands, a festival, a national park gateway, anywhere in high season
- The first two nights, always, because arriving tired and hunting is miserable
- The last night before an early flight
Leave open:
- Accommodation in cities of any size, outside peak
- Regional transport that runs frequently
- Most days of most itineraries
So your three weeks probably contains three or four things that had to be booked and about fifteen nights that did not.
What that buys you is the thing you are worried about losing: staying an extra night somewhere good, leaving somewhere early, following a recommendation. On a three week trip that flexibility is usually the difference between a good trip and a memorable one.