The setting I'm thinking of is in the not-so-distant future where humanity has become an interplanetary species using conventional propulsion. The solar system is largely colonized with human settlements going even as far as TNOs like Pluto.
Along with their settlements, humanity has brought warfare to interplanetary space. Hostile engagements between armed spaceships are similar to modern-day naval engagement and are resolved at a large distance using missiles.
Given the possibility of your ship being fired at having large amounts of air onboard is a significant liability. Air is combustible and escapes fast into vacuum through any significant fracture in the hull. It provides very little in terms of protection for the crew or structural integrity to the ship. Air's only real use onboard is that the human crew need it around them to breath, but that is not entirely the case in modern times and may not be the case in the future. In this setting there exists "liquid life support" and it is used extensively on military vessels built for combat. The crew areas of these warships are filled with a breathable liquid with density similar to water. The rest of the ship is hard vacuum. There is no air onboard.
You may wonder if this breathable water-like liquid is achievable and so do I but I'm pointing towards definitely. It's just a question of engineering either the liquid, of which chemicals with similar properties already exist (perfluorocarbons), mechanical artificial gills, or the crew to have actual biological gills.
Liquid life support provides the warship with a number of advantages. No air means no risk of fire or explosive decompression. The liquid shields the crew from radiation, absorbs more heat than air, mitigates the harmful effects of high-G acceleration and improves the ship's structural integrity.
Downsides include water being heavier than air, limited visibility and hearing inside a liquid medium. Technology could be used to mitigate the latter two and the first one is the reason this system is only used on warships built for brawling and not efficient hauling.
What additional downside could make this a really bad idea or downright impossible?
EDIT: forgot to mention that during normal spaceflight and during routine engagements, these ships have 0 G on board. There is no centrifugal gravity being generated, and gravity is only present during maneuvers. Water pressure would be maintained constant by a system of hydraulics.