Off the beaten path for three days?

I would stay somewhere in Spain for those three days to be honest. Just trying to get to Italy is going to burn through one day. There are a plethora of undiscovered gems close by to Sevilla alone.

In practical terms, which city are you flying out of to get to Athens?

Ditto--you would lose valuable time trying to do it that way. If it was efficient to get to/from Sevilla and Athens, it would not be undiscovered.
Another idea--many, including myself, give Athens short shrift (I figured I'll be back), so in a way, if you are a city person, spending three days in Athens would in a way could actually be "off the beaten path."
What is your itinerary for Spain? There are many small jewels near Sevilla.

Agreed with valadelphia, Athens deserves those 3 days, with all its fascinating history and fantastic museums, if you are already not doing so pre/post cruise.

For sure I'd either stay in Seville (you could take a day trip or two from there; Carmona is nice) or go to Athens early. There's no way on earth I'd want to lose a major part of two days during that short break, and flying on two of those days would be a massive "No" for me.

With a cruise you won't really be in Greece so go to Crete for a few days, stay outside of Chania in the hills.

Don’t add more hassle by trying to keep updated with the Covid provisions of a third country, particularly for such a short stay. Either visit somewhere such as Jerez or Cadiz as a day trip from Seville or go to Athens early.

Thanks for all the information and advice. We will have spent the previous weeks touring Spain, so not thinking we’ll stay there, but the idea about avoiding another country/ Covid protocol is really smart. I’m thinking that we’ll head to Greece and spend the three days there. Chania on Crete sounds pretty good. Again, thanks for the advice.

Is there a direct flight from Sevilla to Athens? Chania would likely require another flight, i.e., hanging out in the airport. Instead, if you are set on leaving Spain, then you could pick up a car and drive to Nafplio in two hours. It's not a bad choice for a weekend if you have no interest in Athens.

Guess you will miss out on all the hidden gems near Sevilla, oh well!

I'll just mention
Cadiz
Jerez de los Caballeros
El Rocio
Zafra
Extremadura