Currently, there are a plethora of qualities to represent neural damage, buggy 'ware, or people whose systems have been thown out of whack, one way or another, by their extensive augmentations. If a character does not take one of those qualities, then I would not apply any of those penalties. Unless your game has the optional rules for buggy second-hand 'ware, cyberware damage, and so on. If so, I hope you also use the optional rules for things like magic loss and acquiring geasa during play, to keep it fair for everyone.
Move-by-wire, like other initiative enhancers, can have long-term effects - generally, this should not come up in play; it is like a character smoking. Sure, in 20 years they might be messed up, but for the time frame of the game, it doesn't really come up. Plus, if the runner lives that long, they will probably be able to afford gene therapy for any problems from their 'ware. One tangible, in-game disadvantage is the move-by-wire, like synaptic boosters, but unlike wired reflexes, cannot be turned off.