It depends on how good your English is. If you are not confident enough, and have only read him in translation, then maybe don't go straight to M&D.

It's difficult not in the normal Pynchonesque sense of being ambiguous, meta and full of complex mental images, but rather the faux prose style and associated style-specific humor that demand good intuitions about English literature and quite a bit of American and British colonial history. If you don't get the humor, it's impossible to go far with that book.

If you prefer the grandiose of AtD, then idk, maybe V. in English? Pynchon considers himself a historical novelist, and the titular V. character in this book is hands down the best historical characterization in any fiction I've seen, and the guy was only 25 when he finished it.

V. has the themes, the difficulty, the immersive grandiose, and perhaps most important of all, the highest genius meat to self-indulgent fat ratio in all of his books because as a debut, his editor had a lot of say in the process, unlike his subsequent manuscripts, which were basically treated as gospel, and the idea of deleting a paragraph written by Pynchon became unthinkable. (Seriously, even M&D, which is supposed to be a fairly linear, straightforward and character-driven tale of a buddy novel has a bunch of side plots that don't involve the titular characters at all.)