Two week trip split up advice

Okay, if you're starting in Frankfort, you will need to take the train all the way to Vienna (farthest away, 5hrs by train from Frankfort) and then travel 3 hrs back to Prague, then either 13 hrs train/9 hrs drive/short flight back to Brussels and ending up in Amsterdam. Frankly, that's one too many cities on the itinerary for my preferred travel pace. You're going to burn the equivalent of a day and a half just getting from city to city. I'd drop one (Brussels?) and reduce your travel time between places.

You'll be making a loop to the south & west to then go back north and east. Flying into Vienna makes much more geographic sense for your desired list of cities.

Everything is a quick flight apart so I don't see the problem with the number of cities. I would do 3 nights each in Berlin and Vienna and 2 nights each in Brussels and Prague. Berlin and Vienna are loaded with museums, food, etc that can take some time to see. Others hate on Brussels, but they have awesome food, one of my favorite breweries (Cantillon), and some cool things to see, as well. Prague is nice, but not worth 3 nights imo

Quick flights are fine, but with the need to get out to the airport, go thru security, and arrive in sufficient time to make a flight, it can make a 3 hr train ride more time efficient than those short flights. In most cases in European cities, the train station is in the middle of town, while the airports are way on the outskirts. So yes, it’s faster to fly in terms of just airport to airport, but it can be a considerable hassle to get to/from the airport. Trains still have little/no security screening and drop you off in the middle of most places.

Op I'd strongly consider skipping Frankfurt and catching a 1 Way flight immediately from there to Vienna or Prague or somewhere else you want to go. You can likely get a cheap flight, you are already there at the airport, and Frankfurt doesn't really correspond with your trip.

That flight will suck for you especially considering you will land later in the day in your final destination and be more tired so your first day is almost a bust. But imo it would be worth it over spending a day seeing a city out of your way you don't care about.

My wife stresses flying, so we fly in Europe as little as possible. A lot better to take shorter or overnight train rides.