Honestly, I think if tone is what's really important than ZeldaXMetroid would be your best bet since Link (certain incarnations of him anyway) and Samus are Nintendo's two most serious characters.
They're still worlds apart. They deal with completely different themes, lores, and concepts. They're built as very different universes.
If I absolutely had to pick the best mesh with Metroid, it would be as others have said: F-Zero. Simply because there's no really significant thematic inconsistencies between the two. Both are science fiction. Both exist in human filled universes with a strong alien presence. Both take themselves relatively seriously. Both, in art design, are more closely interchangeable than anything else.
They could do a Kingdom Hearts type thing. Mario, Yoshi, DK are all one one planet. Hyrule is its own planet/realm. Metroid, Kirby, Star Fox, Pikmin, and F-Zero are all in space. Fire Emblem is its own planet. Pokemon is its own planet. Kid Icarus. blah blah. You have a space-traveling threat and use one or more of the space-traveling Nintendo franchise to connect the ones that don't space travel. Top it off with an amnesia ending.
Yeah. Stuff like Kingdom Hearts, and Smash Bros, exist in a "what if?" universe where the aim is to merge everything together, recklessly even, just to see what happens. A Nintendo All-Stars RPG style thing would work fine with this too, as the ideas is "ITS EVERYBODY! TOGETHER!", and therefore becomes it's own contained universe in a sense.