Specific actors in specific roles, just a few:
Avery Brooks as Sisko and Nana Visitor as Kira Nerys are two that I just don't think any other actors would have worked as well in. Both of them are an absolute joy to watch and re-watch (moreso even than people like Patrick Stewart as Picard, for my money)
David Tennant as Dr Who. Also David Tennant as The Purple Man, just perfect casting.
Peter Falk as Colombo, really surprised no-one has mentioned this yet. It would be such a bad show with almost anyone else in the role.
Andre Braugher as Det. Frank Pembleton in Homicide: Life on the streets. Just amazing. Set the bar for me, TV acting wise, and set it high. Really mad he didn't get more juicy roles like that, though he did clearly have fun in Brooklyn 99.
Ian Somerhalder as Damon in The Vampire Diaries - it's not a great show (though weirdly watchable) but god he makes that a fun character for the first three seasons or so. Nina Dobrev gets kind of a half credit because whilst Elena isn't special, Katherine is delightful.
Archie Panjabi as Kalinda in The Good Wife*. Entire seasons were rescued by Kalinda's acerbic presence, where we'd have been suffocated by the leads otherwise (though Josh Charles was also always a bright spot).
May be back with more later!
* = I must note that Robert/Michelle King seem to be exceptionally good showrunners, as they consistently get really good performances, cinematography, costumes**, set design and even lighting where so many others on similar budgets do not.
** = albeit sometimes on the implausibly expensive for the character side - can an investigator for the Catholic Church really afford a fully-painted custom leather jacket? Hmmmm. I guess I'll let it go because it looks so good. Maybe he's saving tons by living in the church attic!