Both 21 and 28 degree nailers are framing guns. A framing nailer is a pneumatic air nailer designed for nailing the framing structure of residential or wood-framed industrial structures. Framing nailers are about speed and production. They are tethered to an air-hose that is connected to a compressor. They're held more like a staple gun than a hammer and they will sink a nail into wood with a pull of the trigger. The nail track of 21s and 28s are arranged differently.
Framing nailers have a nail track similar to the clip in a firearm. It feeds the nails into the pneumatic piston. The difference between a 21 and a 28 is the angle. If you point the nailing tip of the gun straight down, the nail tracks 21 degrees and 28 degrees respectively. While each gun can probably shoot a variety of nail sizes -- depending on the make and model -- a 21 can't shoot nails of any size designed for a 28 and vice-versa.
Framing nailers don't use individual nails like you'd use if you were hand nailing, and they don't use rectangular rows of perforated wire nails like many pneumatic brad nailers. Framing nailers shoot clips of framing nails that are fastened with two temporary strips of plastic which break apart when the nail is actuated. The nails have to be staggered at an angle to accommodate the larger diameter of the nail's head. The ridge of one nail head laps over the adjacent nail head, allowing them to be packed closer together in a clip. 21 degree angled nail clips and 28 degree nail clips are both standardized in a number of types and sizes, but they are not interchangeable; they will not fit the feed angle of the others' nail clip.
One angle isn't necessarily any better than the other. It's really a matter of personal preference. The make and model of the gun and its overall design and quality are more important than the nail-feed angle. If you have a crew and some are already using one angle, it may be convenient to stick with that angle so you don't mix clips. There can be one benefit to the 28 design; it's a more acute angle. If you're framing gables, tight corners and tricky angles, the 28 has more potential to fit into tighter places, which can be a trick with pneumatic nailers.