Also, if you plan to purchase the added insurance or prepaid fuel, lead off the conversation with that; if the agents know you're doing them a favor (by spending more money, for which they are incentivized), they're more likely to give you a break on your upgrade charge
But, again, members still benefit the most when it comes to upgrades
Alamo/National/Enterprise have a row of cars that are free for any of their members to drive so long as they booked a mid-size or better. The companies use this system to unload cars that aren't rented often or that they might be heavy on. "You'll probably never get a Cadillac when you've booked a Ford Focus," one agent says, "but you might move from that bland Toyota Camry to a Chevy Impala or a small SUV."
On top of that, agencies typically have another dedicated "hot row" for members only, and it's staffed by a personal attendant who can offer a better upgrade than the agent at the counter.
Book as far in advance as possible, then check the rates regularly to see if they've fallen
The best time to book is as soon as possible. Each company has software that links to the online travel sites and adjusts prices according to both other listed prices and the company's available inventory. If it's a holiday weekend or peak travel time, inventory gets booked sooner and rates go up. If you see a great deal several months out, book it, then check every few weeks to see if it has changed and request your price adjustment.