Mmhh, I especially like the 'ground covered by lots and lots of bones' and 'bad stuff happens, when blood is spilled' suggestions. Now to combine them ...
Thirsty Bones
I'd propose, that the area the altar stands in (wherever you place it as by other suggestions) is covered with bones, the implication being centuries of sacrifices. There's one safe way to reach the altar, which the cultists would normally take and which the PCs probably will take, too - when they arrive. Unfortunately while the PC to take the dagger is performing the necessary rites and the sacrifice of his own flesh in order to pick it up without falling victim to Orcus' powers, the head cultists arrive blocking the safe way out and the novices approach from the other sides (spot check to notice they're moving slowly and very carefully).
I'd have the picking-up last several rounds, so there's time for some bloodshed - on the bones of course. Most likely the PCs will try to avoid the cult's elite fighters and flee across the unsafe bone area with most unfortunate results ... the broken and jutted bones function as caltrops, hampering movement and inflicting small wounds. Some of them are poisoned or infectious. Some of the lower level cultists engage the PCs on the bones being mostly slaughtered - and thus fueling the altar's defense. Every drop of blood spilled on the bones makes them come to unlive, the bleached surfaces covering in places with rotten muscles and sinews. Hands, claws, things everywhere, grasping the PC's legs, scratching and clawing. Entangle the Orcus way! For extra shock value have one skull turn into the undead face of some NPC the characters knew at some point, moaning and crying for help. These impediments require strength checks to get past or attacks to destroy them. Each grasping hand or other appendage has as many HP as blood was spilled (damage dealt to a cultist while within the bone area).
Also for every mook that dies one 'blood skeleton' or somesuch rises from the ground with as many HP as the killing strike did damage. While not especially challenging on their own, they try to grapple the PCs and block their way. Even the fighter probably can't cleave them all. Depending on how mean you want to be, these blood skeletons could also contract diseases. Finally if a PC dies within the area, the bone floor convulses as the hungry bones swarm the corpse as would piranhas, stripping the bones bare and adding the poor soul to their ranks.
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The idea is to make the players panic - they may have had tough challenges getting to the altar already, but now that they have the artifact, they can't get way! Combined with the grisly image of the grasping bones around them feeding off the blood of the killed they should be happy to get away, when they finally manage it. Also note the dilemma - the PCs need to get the cult novices out of the way, but killing them strengthens the thirsty bones! Bullrushing and knockdown might avoid this outright, but the caltrop-like ground doesn't make it a very viable option. For additional vileness one of the higher ranking cultists could use telekinesis to slam a (some) novice(s) face down into the bones triggering the rising of blood skeletons and empowering the impeding hands.