Well, you could be running too much bass boost (if you are running any), which could be killing them. Or, even though "the amp is 1/4 of the way up" (the gain control), it could still be too high depending on the output voltage of your headunit and the input stage of the amp. Or, you could simply be pushing the subs too far and over-excurting them.
First; what kind of box are you using. 2nd; What exact models are your subs, amp and headunit (links would be nice). 3rd; What are all the settings (bass boost, gain control, "bass" level on you headunit, etc). 4th; How are the subs blowing.....are the coils frying or is the sub bottoming out or otherwise getting mechanically damaged?