I have a pet peeve about stories with aliens. It's when I read about aliens that are described in loving and extensive detail as incredibly, immeasurably different from humans - and then they have a recognizably human culture. My brain rebels, and I feel I want to apologize to the author for being unable to stay in the story, after this person went to all the trouble to give these creatures the marvelous alien science, the ecology and physiological background. But if I can hardly comprehend the alien physiology, then I feel I should hardly be able to understand their sense of self and culture, either. If I can, there's a problem.
So is the solution to take our lovingly crafted aliens and give them a wildly different culture?
In any SF/F story, it's important to consider the information burden you're placing on your reader. It's not that readers can't handle complexity - in fact, SF/F readers are generally unusually receptive to complexity and difference - but if that complexity goes in all directions, then you have a problem. The story seems to be all over the place.
So ask yourself, "What is my story about?"
This isn't an idle question. It's an issue of focus. If your alien's culture is the central issue of the story, as it usually is with my stories, then there's no point in distracting from the cultural issues by making their physiology vastly different. The culture and the physiology have to match, but they needn't match precisely - as long as the two can fit together acceptably, that's all you need. So I personally try to use familiar knowledge sets on the physiological front, and build the culture outward from there with the quirks that I want to focus on.
On the other hand, if alien physiology is the central issue, then you don't really need that much complexity in culture - just make sure that the culture fits the ecology and the physiology and don't worry about delving into complexity. Of course, there are happy mediums on both sides.
I would say that my story, Cold Words, is an example of a story where culture is central and physiology is matched to it, but kept relatively simple. An example of a story that focuses on divergent alien physiology is the story "Doctor Alien" by Rajnar Vajra (Analog Jan/Feb 2009). In that story, there are four different types of aliens, each of which has vastly different physiology - but Vajra keeps his focus. How? By making the whole point be "we know nothing about these guys and their culture." The alien merchants are a mystery - tentacles are involved - and though their behavior is adapted to fit ours in a highly amusing way, they're capable of unpredictable and dangerous behavior and you'd better not cross them because we don't know how they think. Oh, and by the way, they're asking the doctor about the behavior of three other aliens, each one with a vastly divergent physiology. Here, Doctor, figure these guys out because we don't know how they think. It works brilliantly, because the divergences are the point. They are the puzzle that the doctor has to figure out. The story is focused.
Think about this as you're designing a story. Don't necessarily shrink away from making the world as complicated as you want to, but when you go setting a story there, keep the focus small. I have some very complex aliens that I'm working with now (otters!), and while their physiology is otterlike and thus predictable in some respects, they have more than one major cultural thread that can influence their behavior. I tried to put both together into a story and it got out of hand. So I changed the whole scenario, so that both of the threads are present, but only one is the source of the main story conflict. Only one is really at stake. I can save the other one for later.
Think through the focus of each story you write. If you can keep all of its complexities matching up in such a way that they serve the story's main conflict, then your readers will be able to tell, and be able to follow better.