E=mc^2 is not Einsteins equation.
The equation derived is E^2 = (mc^2)^2 + (pc)^2
If the observer and the object are in the same frame of reference (FoR) and both are stationary relative to each other then p=0, and the equation simplifies to the ever famous E=mc^2 (the negative solution be mathematically valid but physically unreal) which is the one generally used to calcuate things such as energy released in nuclear reactions since everthing is in same FoR and generally isn't moving anywhere.
More later if I can find my physics degree notes and textbooks on this subject (I think they may be unaccessable and at my parents house though).
As for Newtonian mechanics and particularly the kinetic energy of an object being 0.5*mv^2. This is the 1st order approximation of the above if you use the lorentz transform to substitute for the momentum and then one of the mathematical expansions to expand the series (I forget which one).
Newtons 3rd law and conversation of momentum and energy still apply for Trucks hitting bikes, bikes are worse off, they have less mass. Its only a simultaneous equation and can be reasonably approximate for the sake of why the biker dies as a perfectly elastic collision with solid non-deformable structures.
To be really confused consider electric and magnetic fields and how they change in different relativistic frames of reference.
