If just Cities 

Brussels (Brugge,Ghent) - Amsterdam (Leiden) - (Hamburg) - Berlin (Potsdam) - (Warsaw or Wroclaw - Krakow) or (Dresden  - Prague) - Bratislava/Vienna - Budapest - Zagreb - Ljubljana - Trieste - Vernice(Padova, Verona) - Milan - Genoa - Nice (Monaco) - Marseille - Lyon - Paris - Brussels 

spots you may consider Nürnberg, Colmar, Strassbourg,Copenhagen,Stockholm, Cekse Krumlov, Poprad, Split, Florence,Bologna, Livorno, Pisa, Rome, Naples :D

Which are finally the best depends what you prefer? Culture,History, partying, nature, Mountains, Coastal areas. 

Your question is like the old question of how long is a piece of string? 

We all have different ways of creating travel plans using factors such as:

Where do I really want to go on my bucket list?

How much do I want to spend?

How long do I need in a destination to do what I want?

How long do I want to be on a train?

and many more………

Also there are thousands of places that members could suggest based on their experiences and preferences.

So what would I suggest?

Assuming you are starting in Ireland your first challenge is how to get to the mainland of Europe? Ferry to UK and then Eurostar via London, Ferry to France or even a low cost flight on that Irish airline we all love (for price at least).

Then I would simply get a map, a decent rail planner and an accommodation site.

For a circular tour of Middle and Southern Europe there are actually only a few main rail routes to consider, but many off shoots towns to and cities. Down through France from Lille, Paris, Lyon and Marseilles. From there you either go west to Spain or East to Nice and Italy.

Italy then has a Northern net of Genoa, Pisa, Florence, Rome, Naples, Milan, Bologna, Verona and Venice. You could even head south to Sicily.

You can then come back through the alps (3 main routes) to Austria, Germany or The Rhine valley/Black Forest. Fr.om there the way home towards Brussels or The channel ports.

And that is the process to consider.

OOI we started with the concept of cruising on Land, but adjusted to a general pattern of Travel 1, stay 2, Travel 1…..

This gives a day of 4 - 8 hours travelling an afternoon check in, an evening exploration, a full day and evening of exploration/dining, a good breakfast and a steady day of rail travel…..

Another thing we did (in Nuremberg) was stay 3 nights and did day trips to Bavarian towns (Next year they will have a 49 euro train offering full access to all regional trains, buses and trams.) 

Other Cities that could offer the same with day trips using an Interrail pass for high Speed day trips could be Vienna, Munich, Lyon - you can easily travel 100+ km each way in a day

Consider what accommodation would suit you, hostels (not for us), B&Bs (great for one or 2 nights), Hotels (can be expensive so look for deals - we find Accor group have a lot of budget hotels as well as 4 and 5 star - Ibis to Sofitel and Adagio aparthotels and many are near the stations). Finally put at least one self catering apartment or other opportunity to do laundry.

Purely personal opinion, avoid sleeper and overnight trains unless you love the Youth Hostel style of life (couchette berths sleeping in your clothes with3 or 5 strangers) or have a bottomless budget (Private  Sleeper cabins (Very small and minimal facilities) have high premiums that match or exceed the price of an en-suite room in a hotel B&B).

Well, that’s a broad question. You can get thousands of different suggestions .

It all depends on your preference and how you want to travel and when. See as much as you can, or more easy going and get to know the places you stay in a bit better? What’s your budget? Stay in cities, balancing between city-nature or more nature?

Do you want to know very well known places, or quieter and lesser known places?

With a little bit of extra information from you, we can give you a more concise suggestion list ;)