Is modifying life creating life? If you don't believe so, then there should be no problem. You really aren't messing with things in anyway we don't already. We selectively breed, same thing, different mechanics. We may have produced results that nature is unlikely to produce, but the fact they exit makes them "natural".
But, what is "mixing species"? If nature is always mixing DNA, and we can produce a "stable configuration", is it not inevitable (million monkeys) that at some point that configuration will exist in nature? Does the question then become is time-travel ethical? We have just moved to a DNA configuration that will eventually exist in the future. There could a problem with this argument if we assume a gradual change and there are no stable intermediate states. But DNA does not require life to exist and organics rain in from space all of the time. Discontinuities are possible.
If you believe the modification is creating life, the question moves towards religion. Whether starting from the "Spirit on the Water", or pre-built components (DNA), is the concept of "Creator God" valid? If so, is there any constraint that prohibits man and god from being the same or equal? If we are gods, mixing species ethics doesn't matter to gods. From the religious perspective, it's probably unethical. Most myths tended towards bad results, from Greeks to Jews, so we might assume the ethical message was "don't".
For me the question is about balance. Physics allows particles to pop in and out of existence, but only in opposing pairs. Anything is possible as long as the net effect is zero. There are schools of thought that there is something in nature that maintains balance. If there is a disease in nature, somewhere there is also a cure. I don't like the idea of creating a proton without creating an anti-proton. Or creating a bio-weapon without a cure. If we create a new lifeform, we should also create a new predator at the same time to allow maintaining balance. So the species mixing (creating a new species) is fine, as long as you create a specialized anti-species.