Heavily non-mainstream titles are probably ones which they might only have one or two copies of - and they're most likely to be out with someone else. It can sometimes take a while, but not too long, usually.
I've been with Blockbuster for about six months now and never had any quarrels with the service. I tend to get through the DVRAB quite quickly, but even so they always manage to send me something from my (200+) list the same day they get discs back.
I've had no experience of other DVD rental companies but from what others say on here, they can be pretty variable, and will out-and-out delay sending you new discs if they think you're renting too many too quickly. No problems like that with Blockbuster.