We just purchased HelpSpot after doing most of the 45-day free trial.
HelpSpot has all of the key functionality as the other major players in an easy to learn and use format.
Over the trial period, I was constantly impressed by Rebecca (I believe she's their main help desk person) prompt responses to various questions and issues; and the developer, Ian, would often chime in as needed.
HelpSpot's easy to use, and extensive, API allowed us to easily set up an email interceptor to pre-populate information into a ticket from our hosting automation system.
Setting up Live Lookup, which allows our staff to either double check information in the hosting automation system or grab it if it was not pre-populated was a breeze.
We did phone call and email reference checks, and all parties contacted only had good words to say about how HelpSpot saved their company time and money.
As long as you have it on the same physical server, it can have secondary portals to support multiple companies; though I would recommend asking them how many you could set up.
The live lookup feature was easy to set up; and what our tech support staff loves, is that all you need (in our case) is a email address off a valid domain name for it to work. That comes in very handy when creating a new ticket for a customer based on a phone call, work order, etc.