Street Signs
These are the most commonly noticed signs. They tell you the name of the road you are on, and the name of the road that you are not on but could turn onto. They're also one of the most functionally useless sign types, ironically. Street signs tell you nothing except what the road is called at the exact point that it's called that - and in Appalachia, names tend to take sudden left turns where numbers don't, or vice versa.
Deliberately ignore the street signs. Just do keep an eye out for ones that say "dead end" or "no outlet", and avoid those.
Road Number Signs
These are the useful signs. Numbers continue where names do not. Even if they do take random-seeming turns, they'll have useful markings for that, such as the numeral and a big fat left arrow, to indicate that the particular numbered highway is turning left at the intersection. Follow these. Know which one you are on. Keep an eye out for other, bigger signs that list what towns or cities are how many miles down the road; these are referring to the numbered highway with that distance.
Interstate Marker Signs
These are related to road number signs, but printed on blue shield shapes. They can direct a driver to the interstate, using JCT and arrows, or just reassure a driver that they're on the correct interstate.
Mile Marker Signs
Most common on interstates, these signs have absolutely nothing in common with the road number signs except containing numbers. On major interstates, the numbers are listed vertically on a small green sign, where road number signs tend to leave the number whole and horizontal.
Mile marker signs tell you how many miles the highway has travelled from its end point, or from the state line, depending. In most (but not all) states, the exit number correlates to the mile marker number. It is incredibly useful to know which mile marker (on which highway/s) home can be located at, which one your destination is at, and and which one the car is nearest at any given time.
On-The-Interstate Signs
At every single exit of every single interstate, and on most overpass bridges, and really on any controlled access road in the Unites States, there are signs. They tell you what town and road are accessible at which exit, what direction those roads are going, and what the next major upcoming city on the route is. There are also useful signs like "gas" and "food" and "lodging" that list available locations for those things - and on the exit ramp itself, there's usually a follow-up that lists what direction to turn for the thing, and sometimes even what distance to go for it.
This plethora of useful signs is one of the main reasons a lost driver should get to the interstate ASAP.
Safety Signs
Learning to drive in the first place should have covered this. Winding roads, changing lane structures, turns, loops, etc. This includes stop signs. Pay attention and be safe.
Maintenance and Border Signs
Usually on the back roads, and can be pretty wordy. These come in lots of shapes and colors; their content is the important part.
Direct and to-the-point ones are easiest to spot; county and state lines. There are also ones with context - watershed boundaries, DOT (department of transportation) zones, county or city maintenance boundaries. All are valuable. It's okay to slow down and read carefully, but really only the location needs to be remembered, and that only until the next one.
Historical Location Signs
These are usually brown, with white text, most often on a major road or interstate. They're not inherently useful, and can be misleading - such points of interest are rarely staffed or near anything useful like food or gas or phones - but are very easy to use as landmarks or destinations.
Other Text Signs
Read anything that has words on it. If the information helps, fabulous. If it doesn't, oh well, you've wasted nothing.
Signs That Aren't Road Signs
Only flashy, metal, reflective, clearly-lettered or stylized symbols on a geometric shape, bolted to a concrete-sunk pole are legal signs. Hand written, cardboard, business, or any other type of sign is not going to get you un-lost in any capacity - but they can help you find a party, a yard sale, or a McDonalds. Or get you the phone number for whatever weirdo is offering cash for insulin and single-wides, if you're of a mind to talk to them (do not!).