I will preface this answer by stating I’m a totally blind individual who uses Jaws as there only screen reader. I've played around with NVDA as well but have l9imited experience with it. Jaws is the most widely used screen reader at least in the US. If you can only use one screen reader I would pick it with the default settings. Both Internet Explorer and Firefox work with Jaws and both are widely used. Another screen reader you could use to test accessibility is NVDA this is an open source screen reader that works well with Firefox but not internet explorer. I would say if cost is an issue use NVDA with the latest version of Firefox, and if your site is accessible using that setup it will most likely work with Jaws. For a complete list of screen reading software see this
Installing and starting a screen reader isn't enough to do good accessibility testing. You won't know how accessible your site is until you turn off your monitor and unplug your mouse. Getting good enough at using any screen reader to do that will take time. The only sighted people I know that are efficient screen reader users either work for the screen reader companies, or do assistive technology training as their job. So while you can use a screen reader to test your site's accessibility the learning curve for a realistic test is quite high.
