Using Izamal as a hinge
Izamal itself is a half-day, so the smart move is to pair it with something bigger the same day. It sits well positioned between Mérida, Valladolid, and the big Maya sites, which makes it a natural mid-route stop rather than a base you branch out from. Ordered by value:
Chichén Itzá — worth it
About an hour and a quarter to an hour and a half by car southeast toward Valladolid. The most famous Maya site in the world, with El Castillo, the ball court, and the Sacred Cenote, and genuinely worth the crowds if you go early before the buses and the heat peak. Pairing Chichén Itzá with Izamal in one day is a classic and sensible loop out of Mérida.
Cenotes around Homún and Cuzamá — worth it
Within about an hour south and west. This is cenote-rich henequén country: at Cuzamá and Chunkanán you ride a horse-drawn cart on old plantation rail lines to swimmable sinkholes like Chelentún and Bolonchoojol, while Homún has a dense cluster of cenotes you can string together by moto-taxi. A cooling counterpoint to a hot morning in the yellow streets, and less trafficked than the headline sites.
Valladolid — worth it
Roughly an hour and a quarter to an hour and a half east. A larger, livelier colonial town with more to eat, more to do, the Calzada de los Frailes, and cenotes like Zaci and Suytun on its doorstep. If Izamal leaves you wanting a real evening, drive on to Valladolid and sleep there.
Mérida — worth it, but as an endpoint
An hour to an hour and a half west. The regional capital and the obvious place to sleep, eat, and go out, with Paseo de Montejo and a full restaurant and bar scene. Most people bookend an Izamal visit with Mérida rather than treat it as a side trip from town.
Uxmal — worth it, but not from here
The other great Puuc-region site, but it lies southwest of Mérida, on the opposite side of the capital from Izamal, so it does not pair on the same day. Save Uxmal for a separate loop out of Mérida rather than trying to fold it in.
Río Lagartos and the north coast — worth it, but on its own day
The flamingo lagoons and pink salt flats near Río Lagartos sit about two and a half to three hours north, too far to bolt onto an Izamal morning. It is a fine destination in its own right, but treat it as a separate overnight from Valladolid or Tizimín rather than a same-day pairing, or you will spend the whole day in the car.
Honest note: do not build a day around driving out from Izamal and back. Fold it into a Mérida–Chichén–Valladolid line, or a morning of cenotes around Homún and Cuzamá, and it earns its place. The one pairing to avoid is trying to chain two big Maya sites and a town in a single day; you will rush all three and enjoy none.