But with monsters active in the world would the Brands even work in the same way as before?
Sure, why not? Now of course, it depends on what you call "monsters", or what you consider to be the way the Brand works. I don't believe every astral creature out there would be out for them, for example.
True but I don't really see much to Isidro outside of comic relief. Sure he has had his moments (pretty much whenever his back story has come into focus) but his scenes are generally the lightest.
Really? Then you should re-read the story since his introduction and focus on his character, as I think you're really underestimating him. He's a cheerful lad so by definition his interactions are hardly gloomy, but he's had more than his fair share of character development, and his backstory hasn't come up in over 10 volumes now.
Totally but it would be interesting to see the reaction should say Guts party arrive in Falconia with their Brands exposed, given the current relationship Griffiths forces have with the former citizens of Midland (pre-V.36)
Guts can still feel apostles when they're nearby, and I have no doubt that the psychological and emotional reaction to Falconia will be far more interesting than a physical one (pain caused by the Brand) would be.