Take away humanoid aliens, you've excluded even the possibility of Spock, and screw it, it's not Star Trek anymore. Hard pass.
again I said more plausible.
One of the most automatic assumptions needed to make more plausible aliens, is that most humanoid aliens are genetically related to modern homo sapiens. It'd explain why so many societies look and act like humans.
The next assumption would be that there exist ancient aliens who spread our DNA.
You automatically have a set up for a great show. Finding those ancient aliens, or at least evidence for their existence.
Just the same you could easily enhance the Vulcan/Romulan narrative, with having them being space faring for 100's of thousand or even millions of years.
EDIT:
You could keep Spock as half-alien pretty easily. The best way IMHO would be to have Vulcans (and other humanoid aliens) all actually descended from genetically-modified humans. Maybe the Iconians, when they had their galactic-wide civilization 100,000 or so years ago, took humans off earth and modified them to live on other planets. Everyone would still be close enough to interbreed - with some difficulties.
Warp drive is something which is theoretically possible according to some hypothesis.
Pad-to-pad transporting is theoretically possible, as long as you think of it as more 3D printing a new body from the one scanned/destroyed rather than transformed from matter to energy and back. But the transporter was only a thing in TOS because they couldn't afford shuttle landings.
Universal translator would have to be dumped, but I think this is a good thing. More adventures could deal with splinter colonies of humans (or other races already widely known) rather than just introducing a new set of bland aliens every week. And when first contact takes place, there can be
Darmok-style difficulties.
A) It's already canon that humanoid aliens share the same ancestry, I believe it was written into canon in the chase.
EDIT: I"m actually a huge proponent of this idea, but it's far enough from trek that I'm not sure it needs to be branded as star trek.
FYI I wrote out a premise for this before.
WW3 decimates earth. Khan and his disciples leave earth. Using genetic engineering and the best of Earths technologies they form a network of O'neil colonies.
After a few decades the Khannites reject Khan. They splinter off and embrace their own societies. In this example they resemble something closer to TOS aliens, amped up hyper aggressive humans.
Two twin brothers Remus and Romulus form the Romluan empire. A generation later a visionairy named Sarek rejects the fascism of the Romulans and creates his own colony.
One of his deciples Khaless forms a society based on a warriror culture motif.
2 centuries after WW3 Earth has again become space fairing and have once again rediscovered nuclear propulsion technology. Over time they and the vulcans begin an alliance and they create the foundations of the prime directive(which in this case would be something along the lines of banning genetic engineering, and only having regular relationships with augmented populations who have a stable gene pool).
In this context bajorans were bread as an underclass designed to be subservient to the cardassians etc.
It'd also give teeth to the dominion.
B) If you're going the lost colonies route, just have them being Oneil cylinders in the asteroid belt.
C) The simplest explanation for the transporter is that it's a small wormhole/warp bubble.
It can transport you from A to B, but only over short distances, that are largely dependent on a line of sight. Artisitically it's a perfect reason why its usage can be used when the writer wants it and forgotten when they wish it not to be.
To the vast majority of fans a transporter being a warp tunnel/bubble/wormhole changes absolutely nothing about the story.
D) You lose time travel, god like aliens etc. Which I think is a great thing to push the genre forward. In stead of recycling low effort cliches, you have to come up with more complex aliens/situations.
E) I'm not remotely suggesting it, but it'd be interesting if you took something like the movie interstellar and made it more like star trek.
F) I always look to the artistic merits of the story. Is data a better character or worst if he's limited to harder science? Is Picard any less great if he hasn't traveled through time? Are the borg less intimidating if their technology is based more on actual cybernetics?
G) Write down your favorite trek moments. How many of them are dependent on magic?
The once that are based on things like time travel, are those episodes you want to see copied?
Some of the greatest moments in Trek (the borg, Khan, the war with the klingons, the prime directive, star fleet, a socialist utopia etc are not in any shape or form reliant on those things.