Granted, he also struggled in NASCAR (which is, in my opinion, an awful racing series, but driving heavy stock cars that are hard to handle is a difficult task nonetheless), but I think the whole culture there didn't suit him either, just like it was the case with him and F1 before that. Did well in IndyCar, and this is his first team in IMSA driving for Team Penske now, I'll keep an eye on him hehe.
As for Senna, the drivers back then were a completely different breed, but so was motorsport in general. Raw racing, lack of safety, and completely different characters and attitudes. I think it's impossible to tell how certain drivers from the past would do in today's F1, but it's safe to say that it has become very different and has lost a big part of its magic.