Whether to choose Ometepe or Granada with side trips depends on your interests. Granada is a pretty colonial city and has nightlife (some will say it is too touristy) and can be seen in a few hours. A kayak trip or boat tour through the isletas is fun. You don't need a whole day for the isletas. 3-4 hours is fine. That means you could definitely go to Masaya, Lake Apoyo and Mombacho. Friday walk through Granada, Saturday isletas and Masaya. Sunday Mombacho. Monday Lake Apoyo. You won't see many tourists in Masaya and we like to sit in the central park for people watching, walk through streets with hammock makers to the malecon and there is the artisan market (which is quite touristy). The big draw of course is the volcano just outside of town. They drive you right up to the steaming crater and you can walk around an old crater, nice views. Lake Apoyo can be combined with some of the white villages. Catarina for the viewpoint and trails, San Juan de Oriente for pottery... And/or you can go down to the lake where there is a public beach but there are also hotels where you can buy a day pass and go swimming, kayaking... Mombacho is covered in cloud forest. Often cloudy (especially in the rainy season) so views not guaranteed. But the cloud forest is lush with weird plants and you might be able to spot wildlife like monkeys, birds and if you are very lucky a sloth.
Ometepe is a rural island composed of two volcanoes. If you have decent weather approaching the island on the ferry is amazing and you have a view of the volcanoes from many spots on the island as well. You can choose to climb a volcano. Both tough climbs, especially Concepcion but with both you can choose to only go to the viewpoint. Concepcion is active, great views but chances are the top will be shrouded in clouds. Still, it is amazing to be right on the edge of the active crater. Maderas has cloud forest (and if you are climbing Maderas you could consider skipping Mombacho) and there is only one viewpoint. You do this steep, very muddy and slippery hike for the forest, all the plants... maybe wildlife as well (we saw monkeys). At the top you can descend to the crater lake which is also often shrouded in clouds. You can rent a scooter to explore the island or go by bus (hardly any buses on Sundays though) or taxi. There is Charco Verde with a nice beach, a nature trail with wildlife, apparently a new butterfly garden and next door there is fun ziplining with great views. There is Ojo de Agua, a natural spring pool. Kayaking on the Rio Istian. San Ramon waterfall hike. Horseback riding...
So it depends on which of those appeal to you most. I love Ometepe so that is what I would choose but that doesn't mean I didn't enjoy the day trips from Granada. You could go to Granada on Friday, see the sights. (But you could also go straight to Ometepe your day of arrival.) Leave early for Ometepe on Saturday and spend Saturday afternoon, Sunday and Monday on Ometepe. Then leave early on Tuesday like Jose says.