There's just a couple tricky ones in these scenarios.
For me, there's virtualenv and rvm that both mess with shell stuff deeply enough to where running them in fish can be tricky.
virtualenv has good fish support, but never really got rvm working. I ended up going back to zsh after 2 years or so in fish because of small issues like that and realising that so long as I had reverse search I wasn't really gaining much in productivity from fish.
In my terminal I usually have several tabs opened by default in fish, but have another open to the python repl, and sometimes bash if I need something. Easy enough to do.
Imho "source" is an anti-feature. I think instead of "source", you always should create a subshell. It properly encapsulates your modified environment and avoids leakage and confusion. Exiting an environment is a straighforward exit/<ctrl>-D like with any shell. You do not need to remember a special "deactivate" command like with virtualenv.
I swear by subshells. They solve so many problems. People object that they don't let you do environment autoloading on `cd`, though (which I also hate, so... Yeah).