Miami to West Palm Beach with Tri Rail and Amtrak. Amtrak actually makes quite a few intermediate stops so it's not just an end to end run. CSX operations too.
I posted a while back that I would love to see a BART (Bay Area Rapid Transit) DLC, though others said it wouldn't work because it was automated. Still, I love the idea. Here's a link to a previous detailed proposal: https://forums.dovetailgames.com/threads/bay-area-rapid-transit-bart.13781/
which sucks cos then what really forces you to follow the signals ... I mean, in-game... you just follow the HUD pretty much and most of the time can ignore yellows and such, which PTC would not allow, I am pretty positive
SEPTA Paoli-Thorndale route (SEPTA would be a really good get). Stamford to New Haven so we get more of the Northeast Corridor and more Metro North. Brightline Florida (not sure on the city pairs, whatever can work) I'd also like to see a Virginia route but not exactly sure if I want part of Amtrak Cardinal route or Northeast Regional with Charlottesville.