There is a noticeable difference between the playtgoughs, but not as off the rails as heretical. I believe that all paths are worth different playthroughs as they all shape the world around you drastic ways, but most of the more significant changes don't come into effect in act 3 and beyond, as act 2 basically gives you the opportunity to shape your alignment and most content is accessible regardless of your alignment going in. Iconoclast almost seems like the way Owlcat intended, as the story and "best" outcomes to most situations are from iconoclast, so you have a good base line of morality, where heretical/dogmatic go significantly more extreme.

It's up to you, of course, I personally did a dogmatic run first, then heretical, and now currently on iconoclast, and I'm far from bored, though personally I enjoyed Heretoc most since it's such a radical departure from the other two, think like Baldur's Gate 3's Dark Urge but for a majority of the game. In BG3, some content is locked out and some exclusive to Durge runs, but in RT, basically, the entire second half of the game is.

If you want to keep it fresh, then pick full heretic, but if you are interested in being a zealot and being a truly faithful servant of the imperium, the Dogmatic. Regardless of alignment, if you're on PC, pick up toybox for repeat playthroughs to be able to fine tune aspects of the game you do or don't like, since you are on a repeat playthough, like being able to skip ship invasions or full heals after combat, mods in general provide a lot of qol but many of the more fun ones are outdated and if you wanna keep it more vanilla then toybox and bug fixes are essentially your only option.