Ya sea en una isla o en una ciudad grande, lo que más me importa de un destino es poder caminar tranquila.

It means whether it be ... or ... / whether it’s ... or ....

So:

Ya sea en una isla o en una ciudad grande
= Whether it’s on an island or in a big city

It’s a fixed expression used to present two or more possibilities.

You may also see:

• ya sea ... o ...
• ya sea ... ya sea ...

Both are common.

Because ya sea normally uses the subjunctive form of ser.

• es = present indicative
• sea = present subjunctive

Spanish uses the subjunctive here because the sentence is talking about alternative possibilities, not stating a simple fact about one specific place.

So ya sea is basically a set phrase:

• Ya sea en Madrid o en Barcelona...
• Ya sea de día o de noche...

For a learner, it’s useful to remember ya sea as a chunk.

Because each option is presented as a parallel alternative.

Repeating en makes the structure clearer and more balanced:

• en una isla
• en una ciudad grande

That repetition is very natural in Spanish, especially after ya sea ... o ....

If you removed the second en, the meaning would probably still be understood, but it would sound less neat and less idiomatic here.

Literally, it is something like:

the thing that matters most to me

Breakdown:

• lo que = what / the thing that
• más = most / more
• me importa = matters to me

So:

Lo que más me importa de un destino...
= What matters most to me about a destination...

Lo que is a very common structure in Spanish.

Here, lo is a neuter article, and together lo que means:

• what
• the thing that
• that which

So:

• Lo que quiero = What I want
• Lo que me gusta = What I like
• Lo que más me importa = What matters most to me

Using just que would not work here, because the sentence needs a full expression meaning what / the thing that.

Because importar works like gustar in this kind of sentence.

The thing that matters is the grammatical subject, and the person affected is shown with an indirect object pronoun:

• Me importa eso = That matters to me
• Te importa eso = That matters to you

So here:

• lo que más me importa = what matters most to me

It is not saying I matter.
That would be importo in a different kind of meaning, but that is not what’s happening here.

Here de means something like about, in, or when it comes to.

So:

Lo que más me importa de un destino
= What matters most to me about a destination

The singular un destino is generic. It means any destination / a destination in general, not one specific destination already known to the listener.

Because poder caminar means to be able to walk, not just to walk.

That difference matters.

• es caminar = walking itself is what matters
• es poder caminar = having the possibility/freedom to walk is what matters

In this sentence, the speaker is saying that what matters most in a destination is being able to walk around freely, comfortably, without worry.

So poder adds the idea of ability, freedom, or feeling safe enough to do it.

Because tranquila is describing the person, not the way the walking is performed.

• caminar tranquila = to walk while feeling calm / at ease / unbothered
• caminar tranquilamente = to walk calmly

The adverb tranquilamente focuses more on the manner of walking.
The adjective tranquila focuses on the speaker’s state while walking.

In this sentence, the second meaning is more natural: the speaker cares about being able to walk around feeling calm and safe.

This adjective-after-infinitive pattern is very common in Spanish:

• volver contento
• salir sola
• vivir tranquilo

Because it agrees with the speaker.

The sentence implies that the speaker is female, so she says:

• caminar tranquila

A male speaker would say:

• caminar tranquilo

So yes, this adjective gives you information about the speaker’s gender.

Mostly calm / at ease / unworried, but in this context it strongly suggests a feeling of safety too.

That is why this phrase can feel a little broader than just safe.

Compare:

• caminar segura = to walk feeling safe / secure
• caminar tranquila = to walk feeling calm, relaxed, unafraid

In real use, tranquila often implies that the place feels safe enough for the speaker to relax.

Yes, you could, but the nuance changes.

• poder caminar segura = emphasizes safety/security
• poder caminar tranquila = emphasizes peace of mind, though safety is still implied

So the original sentence sounds a bit more personal and emotional. It is not only about danger; it is about feeling comfortable and unworried.

Both are possible, but they are not exactly the same.

• una ciudad grande = a big/large city
• una gran ciudad = often a great city or a major big city

In many contexts, gran ciudad can sound a bit more set or more elevated, and sometimes it carries the idea of importance, not just size.

Here, una ciudad grande is the straightforward, literal choice: the speaker is contrasting an island with a big city.

The sentence is built like this:

Ya sea X o Y, lo que más me importa de Z es A.

In this case:

• X = en una isla
• Y = en una ciudad grande
• Z = un destino
• A = poder caminar tranquila

So the pattern is:

Whether it’s X or Y, what matters most to me about Z is A.

This is a very useful structure to learn because it appears often in natural Spanish.