Ergonomics:

the weight and shape of the pen, plus the material it's made of, determine how the pen feels in your hand.

Some people prefer lighter pens, others prefer the feel of a hefty pen. If you're writing very quickly, a lighter pen won't tire your hand as quickly, but a heavier pen will give you more control.

Some pens taper from a thick barrel to the writing point (Parker jotter), while others have a straight barrel nearly all the way to the writing point (Cross century). Other pens will have a rubber grip above the writing point (pilot g2, uni ball signo 207, and most plastic ballpoints). The shape all comes down to personal preference, which is usually decided by the size of your hand and grip technique. However, I have heard people claim that a thicker pen takes less effort to hold, therefore it does not tire the hand as quickly.

Focusing on the grip, pen materials usually fall into one of 3 categories: rubber, plastic/resin, or metal. A rubber grip is lightweight and tactile, which makes the pen easy to hang on to. However, it does increase the thickness of the pen, which may deter people who prefer a thin pen. Plastic/resin is also lightweight, but doesn't offer as much friction as rubber. In my experience, resin doesn't get terribly slippery when sweated on compared to plastic. However, it's mainly used in high quality fountain pens. Metal pens typically have the least grip of the group, but can be finished with grooves or a good brush job to increase friction.

Ink and ink delivery system:

this is the type of ink and how the ink gets on the paper.

Ballpoint: ballpoint pens use an oil/alcohol-based ink. If you've ever cut open a ballpoint pen in elementary school, you'll notice that it's very gluey. ballpoint pens are the least likely to smudge/smear/bleed, and cheaper ballpoints will need a bit of encouragement to move across the paper. putting pressure on the pen to write is what tires out the hand

Rollerball: rollerball pens also use a ballpoint tip, but have a water-based ink. they move much more quickly across paper, and create a fairly clean line. as such, they require much less pressure to put ink on paper. however, they are prone to some smudging/smearing/bleeding.

Gel Rollerball: similar to the liquid ink rollerball, except the ink has a higher viscosity. This means it doesn't take much pressure to write, but is unlikely to smudge like the liquid ink rollerball. these pens can also create much thinner, cleaner lines due to the gel ink's higher viscosity.

Fountain: the fountain pen uses a free flowing ink cartridge, and a solid nib to deliver the ink. I believe ink flows into the paper through osmosis (the paper being porous and "sucking" the ink from the nib), but don't quote me on that. fountain pens take absolutely no pressure to draw ink, and move smoothly across paper. I think if you're getting a tired hand, a fountain pen would solve the problem. However, fountain pens do require you to refill the ink. pens like the twsbi eco or twsbi 580 have huge ink resevoirs and rarely need to be refilled, whereas the metropolitan or safari can take ink cartridges or be converted to use a piston resevoir.

Felt tip: felt tip pens use a spongy cartridge that is soaked in ink, and then delivered to the paper through the hard felt writing end. they require very little pressure to draw ink, but more effort to move the pen across the paper than a gel or rollerball. they are typically all plastic construction. a bold felt tip pen is often called a "sign pen".