Suggestions for First Time Europe Itinerary

So that means you'll have 20 nights to fill if I'm not mistaken. It's not too late to experience some Swiss mountains. Italy, Brussels and Amsterdam would also work. But don't try to see to much. Maybe a loop Berlin-Prague-Vienna-Switzerland-Lyon-Paris. You could also add a bit of Italy if you want.

Focus on one of two places! You will return. My first trip was London and Switzerland.

You might enjoy the French Riviera and Cote d'Azur. The mountains and the Mediterranean in Southern France provide great scenery. You could take the regional train from Nice to Villefranche sur Mer, St Jean Cap Ferrat, and Monaco. You could also go to Paris by train from Nice at the end of your trip. We went in early October one year and loved that area.

There are a number of resources on this web site that may help you to focus on areas that fit your requirements.

You can look at the maps and itineraries of the various RS tours to get a better sense of major tourist areas as well as more remote scenic areas, and towns off the beaten tourist track.

https://www.ricksteves.com/tours/index

For train travel info, look at the pages covering rail passes - not that you should necessarily use a rail pass, but rather that the maps for each country will show the various rail connections that are available. That should help to link trips from one destination to the next.

https://www.ricksteves.com/travel-tips/transportation/trains

Do either of you speak a foreign language? You may want to consider how you would function communicating in an area where little English is spoken. Even in Berlin, where English is widely spoken, you will find times when you need help, or a translator app, just to read a menu to order breakfast. So a location like Prague may be more challenging, especially if you haven't been to Europe before.

Finally, RS guidebooks are invaluable for trip planning, once you've defined a basic itinerary.

I have been all over Europe and lived in Germany for four years.

If you arrive in Berlin and depart from Paris, then I suggest an itinerary that avoids flying within Europe (you waste time in airports).

Options are many:
1) Since you mentioned Switzerland, one choice is going via Switzerland. It is a very scenic country, even though one of the most expensive in Europe. From Berlin, proceed to Dresden, then to Prague (Czech Rep.), then to Nuremberg, Munich, Salzburg (Austria), Garmisch/Fussen, Germany, then on to Switzerland. Lucerne is a must see. Consider Interlaken, with its wonderful location in the center of the country. Then consider Geneva, Switzerland or Bern, Switzerland and then Strasbourg, France. From either Geneva or Strasbourg, proceed to Paris.

2) Another option from Berlin is still down to Dresden, then Munich, Augsburg, then take The Romantic Road https://www.romanticroadgermany.com
that includes some small cities and towns with the original medieval walls and buildings. From Wurzburg, proceed to Cologne on the Rhine and head up toward Amsterdam. ( you could head for Frankfurt and then turn north, taking a short cruise on the Rhine, passing the Loreli. From Amsterdam, do a tour to the countryside (after some days in that city visiting the Anne Frank house and the Rijksmuseum), then proceeding to Belgium with a day in Brussels, but especially to see Brugges and Gent. Don't miss Brugges.
From there you can head to Paris.

I started down the trail of recommending destinations and then thought to try on your jogging shoes. Hence the recommendation to dabble in google research for runners travels in Europe. A simple mix of key words found a number of interesting sites, even for this non-runner, so suggest following your fellow travel exercisers guidance on places they have experienced. Following is a one link that may be of interest:

https://longruntravel.com/best-running-holidays-europe/

Pack light!

Thanks for the suggestions: I think I'm getting close to a decision, after several months. I think the suggestion to avoid air travel as much as possible is a good one. a 5 or 6 hour train ride is probably quicker than a 1.5 hour plane flight when you factor in the travel to the airport, arriving early, check-in hassles. Air travel is one of my least favorite things to do. My semi-final itinerary is:
5 nights in Berlin for the marathon.
2 nights in Munich for Oktoberfest experience.
2 nights in Lucerne with perhaps Mt. Pilatus day trip.
4 nights in Interlaken with possible day trips to Jungfraujoch, Grindelwald / First, Lauterbrunnen Valley.
2 nights in Zermatt with possible day trip to Gornergratt
2 nights in Milan.
3 nights in Nice
2 nights in Lyon
5 nights in Paris

I have an old friend who lives in Nice and that's why the detour South. Not sure if that's too much to add.
The good thing is that we can take trains throughout and hopefully, weather permitting, see some wonderful scenery in both Switzerland and France.

I would welcome any comments or suggestions since this part of the world is totally new to me. Thanks!

Milan and Nice can be skipped. They are not as scenic as other destination cities.

If you are interested in Oktoberfest, then book your hotels early.

Nice can be useful as a base to explore Cote d'Azur- including Monaco and the charming hill towns. So plenty to see while you're visiting your old friend.

Instead of staying in Interlaken, I’d stay up in the mountains in Mürren, Wengen or even Lauterbrunnen itself (valley).

Still on the subject of Nice...

If you didn't have a friend in the area, I'd recommend you skip it this time. Not because it isn't worthwhile (I like that area a lot), but because most people who go to Nice want to see some of the coastal towns and one or two of the hill towns. Three nights (not much more than 2 full days) would be inadequate for that sort of experience (though it will help if you want to skip all the art museums in Nice and surroundings), and you're following Nice with just two nights in Lyon, a city with a lot of varied and rather scattered sights. I'd consider even three nights in Lyon rather short.

Both the Milan-Nice leg and the Nice-Lyon leg will be about 5 hours by train. I'd give some thought to tweaking the stops between Interlaken and Paris in order to spend less time sitting on trains.

I have a vague recollection that the weather in Zermatt may be particularly iffy, with short stays there being not advisable, but my memory could be wrong on that point.

There's general (though not quite unanimous) agreement that Interlaken is not the best place to stay in the Bernese Oberland. Almost everyone seems to prefer a higher location--at least Lauterbrunnen if not somewhere like Muerren or Wengen. I don't know that area at all, but I've read dozens of comments on the topic of where to stay there.

Two nights in a city the size of Milan may not result in a great experience. I'm looking forward to spending substantial time there because of all the Art Nouveau architecture, but it seems that most folks just blow through the city as fast as they can, seeing The Last Supper (if they can manage to get that difficult ticket) and the Duomo.

Don't stay in Interlaken! Spend an hour or two exploring if you want, then head to the mountains. The Berner Oberlander is just about the most beautiful place I've been while Interlaken is....fine.

I'm a cyclist and hiker. You'll get a fantastic combo of running, hiking great food and culture in the Dolomite Alps of Northern Italy. You'd go from Berlin to Munich first. Then the trainline between Munich and Venice via Innsbruck Austria and Verona is about 6 hours of travel time. Along that relatively efficient route you will take in an outstanding variety of cultures in a superlative natural setting. You can stop along that route to stay many times and still get off the train someplace interesting.

The other thing that's good about these South slopes of the Alps is that unlike a lot of Switzerland they are protected from early season weather systems coming from the northwest. Probably you'll get good weather in Switzerland in October, but your chances are even better on the south side of the mountains.

https://www.mensjournal.com/adventure/trail-running-in-dolomites

https://www.brixenmarathon.com/en/

Anyway, You could do a lot worse than flying into Berlin and flying out of Venice. You'll see both many famous cities and gorgeous more rural areas too.

I think your plan looks perfectly fine if you don't mind a few longish train trips.
Berlin-Munich 4 to 4 1/2 hours depending on whether you get a Sprinter or a regular ICE.
Munich-Luzern 4 1/2 hours with the ECE train to Zurich then change to Luzern.
Milan-Nice 5 hours with an IC train to Ventimiglia then change to Nice.
Nice-Paris 5 3/4 hours with a direct TGV.

Re-emphasize booking a hotel in Munich now as they are already expensive.
Re-emphasize staying in Wengen, Muerren or Lauterbrunnen when you visit the Berner Oberland.
Zermatt is fine. maybe you can decide to skip if the weather looks bad. It will be shoulder season in both the B.O. and Zermatt, so I think you can be flexible there. It is 4 1/4 hours from Muerren to Milan.
Nothing wrong with 2 nights in Milan if you want to see the Duomo or the Last Supper.
Notice I left out Lyon. I think you can afford to skip it to leave more time in Nice, and you have a friend there.