Seeking Transportation Advice for Upcoming Trip to Spain and Portugal

If visiting Sevilla (Seville) in Spain (ES), you can take a direct bus from Sevilla to Tavira, Portugal (PT) that takes 2h. Where in ES and PT are you going?

What cities? The cities you are trying to travel between would have a big impact on the best mode of travel

The best option is to take the train, or a coach or fly, depending on which cities you want to travel between.

The cities that I have narrowed down so far are Lisbon, Madrid, Barcelona, Seville, Porto, and Granada.

What are alternative modes of transportation other than flying between any of these cities? I am also open to adding another city so that I can get to one these from there.

Train and bus travel will not be convenient between the two countries so you’ll need to fly. I would also fly if traveling between Barcelona and Granada because it will take up an entire day since there is no longer an overnight train. However, a direct train between Granada and Madrid takes 3h 45m: https://www.renfe.com/es/en.

You can use the bus and break up the trip so it's not one long slog. I like the looks of the Sevilla-Merida-Lisbon route myself but I have not done it ( I had a car in the area).
Where are you flying in and out?

Thank You for all your responses.

I've narrowed it down somewhat. I want to go from Seville in Spain to a city in the Algarve region in Portugal. What bus ride is the best option and for which city in the Algarve region?

Either use Alsa Bus or Flixbus from Seville to Faro, then train to Lisbon.

Both companies do also run through buses from Seville to Lisbon.

It is also possible, although a long way round to enter Portugal from Spain via the Ayamonte cross river ferry. That is an all day affair. Bus to the ferry on the Spanish side, train on the Portugese side.
That was the old way before the international road bridge was built.