I rent cars all the time for hubby when he is on the road. We spend about $1000 a month on rental cars due to our company business travel, etc.
We now have a corporate rate with several companies as well as the frequent renter program and that helps the overall costs. Right now I use Thrifty a lot. We'be had good experiences with Alamo as well. Hertz is probably the most expensive.
Remember to ALWAYS make sure you have unlimited mileage and make sure there are no clauses that say the car cannot be driven across a state line.
IF you have to drop off in another location, make sure you ask upfront. ONE time, I did not ask up front and by chance, hubby had an emergency and just drove to the next location. That costs us an extra $700 due to mileage in another state and drop off in another state.
Don't buy the extras as far as insurance,etc. Your personal insurance covers you as well as MOST times the credit card you use to rent the car. SO that $$ is just gravy to the rental companies because they know they can scare many people into accepting it.
Renting to and from a good airport helps cut costs. Also, if you are in an outlying area, sometimes Enterprise has good deals and they do come pick you up.
Good luck! Once you do it a couple of times it will be second nature to you!