Elizabeth didn’t seem to completely rule out a romance between Fitzsimmons. This excerpt from an interview with TV Guide is from Oct. 2013.
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Simmons and Fitz have this brother-sister, love-hate relationship, but is there really nothing more there?
Henstridge: My mom told me when I was super young, "If boys hate you, it means they like you, don't worry." Maybe. There's always going to be a possibility, I guess, because they're so close and really understand each other, but definitely for right now, I don't think you could convince either one of them that they are meant to be together romantically. We'll just see. We're told fairly little. I love that because it just means you're in the same headspace as your character when you're playing them and you're not trying to hint at anything else that comes down the line. I love that they are brother-sister right now. If anything romantic happens, I could see it happening, but I like that, for Simmons, it's not really her main priority. I don't think she even knows that could be a good idea.
Agents of S.H.I.E.L.D.'s Elizabeth Henstridge: Fitz and Simmons Are "Like a Married Couple"
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My interpretation of Fitz’s crush on Skye was that the writers intended it to be brief, lighthearted, and comedic whereas the storyline of Fitz’s feelings for Simmons was meant to come off as longterm, deep, and even heartbreaking at times.
Also, I didn’t view Fitz’s crush on Skye as something that lasted throughout the majority of s1; I saw it more as a schoolboy crush that was nipped in the bud halfway through 1X06 not during the pod scene of 1X22. I believe that for Fitz there was a shift away from a sibling-like relationship with Simmons during the episode FZZT. About halfway through that episode and onwards, I no longer noticed him trying to gain Skye’s attention/affection. For the remainder of the season, his focus was on Simmons.
Furthermore, I didn’t see the pod scene between Fitz and Jemma as something that appeared out of left field. There was a build up (which included great moments of concern for each other’s safety, jealousy, hugs, longing looks, etc.) that culminated to that highly emotional moment in the pod.
Even Jed and Mo stated that the underwater pod scene between Fitzsimmons was planned well in advance -seems like even before the pilot was shot.
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When you talk about character moments making the biggest impact, I immediately think of Fitz and Simmons saying good-bye underwater. Why did you want to take their storyline that way?
MT: When Iain and Elizabeth screen-tested for us, way back when, the scene that sealed the deal was a scene that was basically what these pod scenes were built out of. It's a very emotional scene where we see the intricacies of their friendship and it was important to actually show that at some point, so we were very happy we were able to map out a story that could land at this place in the finale.
JW: When they initially auditioned, there were a lot of funny scenes, and when we wrote the emotional scene it was just to make sure they had the ability to pull it off, and both of them broke our heart when they auditioned. They have this brother–sister inseparable feeling between them, but we wanted to evolve Fitz past that and have him break your heart in a different way. We shot those scenes very quickly and they just absolutely nailed it. X
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It’s my belief that if Fitz and Skye had been the intended couple, then it would have made sense for the showrunners to have tested Iain and Chloe’s chemistry. However, he auditioned with Elizabeth while Chloe auditioned with Brett. Jeff, Jed, Mo, and Joss are pros; they
knew what they were doing when they screen-tested Iain with Elizabeth and Chloe with Brett.
On another point, if Fitz’s attraction to Skye had played such a prominent role in his storyline throughout the majority of S1, then surely
at some point Iain, Chloe, the writers, etc. would have been asked about a Fitz/ Skye relationship; instead Iain, Elizabeth, and the showrunners dealt with countless of inquiries about the Fitzsimmons dynamic. Besides, if Fitz/ Skye had been the intended couple, I’m sure the creators of the show would have been, if not openly pushing it,
at the very least, mentioning this pairing in some sort of light during interviews in order to plant that seed in the viewers’ minds. Perhaps I just haven’t stumbled upon those interviews yet.
To me, there is just far more evidence out there that points towards a calculated planning of a Fitzsimmons romance by the writers during s1 than there is for an intended genuine Fitz/Skye pairing. While it may not be your cup of tea, it is what it is.