I have used all of the major national companies with minimal problems. Don't be afraid to tell them if a car won't work for some reason. Last time I rented a car in Las Vegas it smelled slightly of cigarette smoke despite being a non-smoking car. It wasn't too bad in the shade in the parking garage so I figured I could live with it. When the next day rolled around, I found that it absolutely reeked of smoke as soon as it started warming up and got worse when I cranked the AC. Between the heat when I was out of the car bringing up the stink and the AC making it worse it managed to get pretty bad, and I was driving all day. I was stuck in a stinky car the whole time as I couldn't get back to switch it out with a clean car. So if you find something you think you can live with for the rental period, think about how bad it will be if something makes it worse and you are stuck with it.
Otherwise, watch for bogus fees. I rented a car from Budget two weeks ago and only put about 60 miles on it over the weekend. I looked at my return invoice and they charged me $13.99 for gas even though I filled up the car. When I complained about it, they told me they always charge that much for gas on rentals if they get less than 75 miles on them as they can't easily see if it has been filled. The fee was refunded without question when I complained which tells me that they just charge this fee and hope that people don't notice that they are getting overbilled. I had to wait in line inside for 15 minutes to get it refunded. Good thing I was early for my flight anyway. I will never rent from them again if I can avoid it. Unfortunately I travel enough for business that I may get stuck with them again at some point.
As others have said, be sure you note any preexisting damage to the car. Some places have policies that things like scratches at the bumper (luggage scratches) won't be noted or billed, but I prefer to cover my rear and make them note all damage.