I think since I can personally relate more to Stella's backstory, it makes it all the more tragic. Although, the four listed here have had to go through their own sets of struggles.

Despite it all I was thinking about picking Bloom. Because losing your entire planet dreadful. However up until the age of 16 she didn't even know about that, much less that she had other parents. One can't be upset about something he/she doesn't know of.

Now I'm not saying one sorrow cancels another sorrow out but even after finding out the truth I can't imagine that missing parents you never knew is more painful than missing a parent that you knew for a long while (as Musa did).

Furthermore Bloom seemed to have a very happy childhood with extremely loving adoptive parents who treated her like their own to such a point where she didn't even have a clue that she was adopted. That's saying something. Where Musa probably felt her dad's melancholy the whole time.
She probably had such a happy childhood until her mom died. And that probably makes it worse. She probably often looked back on the happy times with sorrow because she misses them so much. She was so happy in the past it made her unhappy when things changed. And that really hits home for me.

Again not to say that the others didn't have it rough on some level. But I think Musa's loss hits the hardest because it is the most final and the biggest kind of loss. With Stella at least she can still talk to both parents, at least there's always that bit of hope. Layla was (without a miracle) able to make friends eventually. While that's still hard I feel like she still got some play in, a real childhood.

And like lovebaltor said, I think the scale in which I can relate to Musa (though my mom is still alive) is what has me picking this.

1. Musa

No doubt that losing your mother is one of the biggest losses ever. Its very difficult without a mother in early age or may be forever.

2. Stella
Stella's Parents were divorced. Mine are estranged. So I can feel what she feels. If I ever had a Sirenix Wish. My Wish would've been the same as Stella's

3. Aisha
I think her her life was empty but not rough. so I place her 3rd.

4. All the same reasons given by @zanhar1

I was originally going to go with Bloom, but even though what happened to her biological parents (and her home planet) is heartbreaking, she wasn't aware of it for a long time and her adoptive parents seemed pretty great. So even though she faces some tragedies later, I expect the majority of her life has been very good.

But the fact that Musa actually lost a parent (and at such a young age) puts her at number one for me. Don't think I really have anything to add that's not been said already.

Stella comes in second. My parents are still together, and I can't imagine what it's like for a kid to have theirs go through a divorce. Once, my own parents had a very intense argument/falling out over something personal. They didn't speak to each other for a whole day, and I just remember feeling really sick and dizzy and having no idea what to do the whole time. They patched things up the day after, fortunately. Anyway, it was enough of an experience for me to accept that there's no way I can know what it's like for someone whose parents really do split up.

I imagine Aisha's lifestyle was more annoying than rough. I still feel sorry for her though.

I agree with @zanhar1 and @FanNoOne111 and @glelsey...
Same reason and it already mentioned above why I choose Musa...Stella second,Aisha Third.

Musa's childhood is definitely the most tragic one.She was just a little child when she lost her mother and seeing her father filled with so much sorrow made her even more sad.

physiologically, this would cause some serious issues.
she's obviously an extrovert, which makes matters worse.

humans are a herb/pack species, we need people, especially from a young age. starving a extroverted child from pairs and social contact its actually considered child abuse.
causing social disability, depression, and general anti social behaviors.

the stress her parents put on her would only cause this shit to skyrocket.
Stress will wreck your body and mind,
it can cause insomnia (lack of sleep) with will commonly turn an adult kookoo in a matter of weeks?

it basically forces them into becoming an outcast and social reject.
things like loss will heal, its the mind craving something (is very similar to what drug addicts go through)
while a mental abuse like this will have been downloaded into Aisha's head at a young age and is virtually incurable.

in many cases in history it was commonly used as torture.
in conclusion, if this was real life she would be so defective she would probably be in a mental asylum.