Fly out of Lisbon or Porto

Lisbon. From Porto you would fly through Lisbon back to PA.

Thanks, JK. So then we would fly from Seville to Porto, right. Spend a few nights there then train to Lisbon for a few nights and leave back to PA from there, right? Appreciate the help.

You will have to check flight possibilities for the season you are traveling.
I fly out of PHL, and a direct flight to Lisbon was not available in late March, I had to connect in Madrid. There was a direct flight back to PHL from Lisbon at the end of my trip in April.

As others are saying, Lisbon likely has more choices for direct flight to Philadelphia, or at least the US. Porto may as well, so check, but usually, from Porto means an early morning flight to somewhere in Europe, a layover, and then on to the US. Lisbon, in theory, should be more leisurely, though I have heard numerous reports about long security lines at Lisbon.

If traveling to EWR is a possibility, during peak season United flies to both Porto and Lisbon and TAP flies to both places year around (with more than one flight a day sometimes)

Open jaw ticket (flying into one and flying out iof another) does save you travel time, transport cost and last night of hotel. That could with lower fare from EWR compared to PHL may make it worthwhile to fly out of EWR.