I have two primary steeds .. a ~2006 K2 roadbike with a Truvative crank (with Truvative's wierd bottom bracket), and a ~2006 no-longer-in-business mountain bike, aluminum frame, deore bottom bracket and crank. I am amazed how smooth the old JIS/square taper seems. I beat the poo out of the mtb, and it just goes and goes. The K2 on the otherhand, is my daily driver. It seems as though the crank is constantly coming loose (enough so that under a full out sprint the chain grinds the front derailer occasionally), and has much more movement in it.

So -- Is there something I can do to keep the crank bolt from loosening? Should I just replace it with a decent square taper bottom bracket/crank?

you could try the blue tread lock on the bolt to the drankarms. and make sure the bolts are up to torque. you may also have some flex in your bb which will cause the chain to rub on the dérailleur.you could change your bb , if doing this you might need to change your cranks too.

Do NOT do this. Proper torque and grease is all you need. Chances are if you've ridden your crank while it's loose, and it's doing it repeatedly - the crank will be shot. Your only option is to replace with a new crankarm if that is the case.

Have had no problems with ISIS cranks/BB's on two bikes.

Yes, but the crank arms have to be torqued to spec when installed. If done right, they should never loosen or require Loctite.