This is a question that I've often pondered. It really depends on who you are, and what you want, but I do have a definitive answer for you... sort of. I hardly ever traveled as a young person, but once I got into my 30's I aimed to take advantage of the travel benefit afforded to me as a hotel worker.
My answer is simple. Take public transit. It's a great way to get to know a different city; it is true that not all cities have great public transportation systems, so you will have to research that aspect. Public transportation is normally very affordable, and there is always either a passenger, driver, or security officer available to help you with directions and information.
I've had nightmarish scenarios involving car rentals. This is the option, however, that provides you with the most flexibility. This may be your best option if you have money and or credit. There are many problems that can arise from this option. Renting a car can be much cheaper than using a town car, cab, or Uber, and save you more time to enjoy yourself, but it can be problematic.
If you have a credit card, you're golden, if you have a debit card tied to a bank account with at least $1000, you're golden. If you are using a prepaid debit, which I have done in the past, you can have issues when arriving at the car rental agency. They may not let you even rent a car. These agencies do not like prepaid debit cards like Netspend. These god damn places sometimes hold huge deposits on these debits. Just be on the lookout.
Last and least is Uber/Lyft/Cab/Town Car. Uber and Lyft may be a good option for simply getting from and to airport, but relying on them to drive you around will kill you, unless you can afford it of course. Cabs are absolute scams, and Town Cars tend to undercut cabs by about 15 percent while working a kickback system with hotel front desk workers. Of all these options, go with Uber or Lyft.
Personally, I prefer public transit, you see more, you meet more people, and it's less costly, but you can't do it in many small cities, so always research.