Mark the destinations on your map in different colors so you can easily determine their priority. On your calendar indicate your arrival city and the date that you land there. Do the same for your departure city and date. Hopefully, you will have date flexibility in some or all of your MUST destinations. Once you've accounted for all of your date committed MUST Go To items, you've got the framework of your trip schedule.
Every person reacts differently, and some react differently on different trips.
If possible, plan fewer activities your first few days to allow your body to recover. Your calendar and map now indicate your MUST Go To base cities. Where possible, use your base cities to stay-put a few days and visit your Would LOVE to Go To and Would Be Interesting destinations by train as day trips. You might also want to use your hub as a pick-up point for an auto rental, driving to some of your selected destinations. You may find, once in Europe, your exploration and discoveries take you to places you had not planned to visit.