I think that severing limbs (where it's a non-trivial thing; we're not talking lizard tails or troll fingers) should be reserved as either a) an alternative to death; or b) a cost that yields a corresponding benefit.
Back in 1e days, I used to rule that PCs who were "killed" by an attacking blow could instead opt to lose a limb or suffer some time of other debilitating injury instead. The benefit was that a raise dead or resurrection spell wasn't required; the cost was the mechanical penalty for adventuring with a severed arm, gouged eye, or whatever until a cleric with regenerate (a pretty powerful spell in 1e) was located.
For 4e, I'd obviously allow a PC who deals the killing blow to choose an effect other than killing the opponent (as I've allowed since 1e; you never, ever have to kill an NPC unless you want to). As for PCs sustaining limb loss, et cetera: I guess it depends on the availability of magical healing. In my current game (Iron Heroes with some D&D-ish tweaks), healing can only be accomplished by rare, highly-skilled and/or blessed individuals (think Elrond, et cetera); such healing is at a level far beyond that of pre-modern medicine (and in some ways modern medicine), but isn't capable of doing "high F/X" things like regrowing limbs or resurrecting dead PCs.
Thus, the only way I'd inflict such an injury on my PCs would be as an alternative to death; if a PC falls and fails his save(s) to die, then he can instead choose to "just" lose a limb. As an alternative, I would certainly allow a player to elect that he lost a limb, eye, et cetera in return for some corresponding reward. What I might do in a hypothetical 4e campaign is allow a player to state that his PC, during a giant encounter, had his lower leg chopped off. This would inflict a speed penalty, and perhaps grant the PC an extra healing surge or two (he's proven himself to be *extra*-resilient and able to fight through pain) or some other ability that was mechanically sufficient to offset the penalty. In all likelihood, I'd still link limb loss to dropping into negatives, at least: People don't really stay in the fight when they've lost arms, legs, eyes, etc.