The weirdest thing about a modern Holmes will be how much forensic science has advanced - as seen by that whole industry of such shows. At the time of their first meeting, Holmes' invention to definitely identify blood stains was considered revolutionary. I can't remember if fingerprints appear in any of the Holmes stories -- probably the very late if any.

That's the biggest change between a Victorian and a modern Holmes.

On the other hand, the first words between Holmes and Watson will play extremely well in today's context.