Edward IV decides against marrying a "Mere widow of England." So Enrique III takes the opportunity to get rid of his troublesome half-sister by making her Queen of England. Another part of the POD is that Isabella's only full sibling, Alfonso, Prince of Asturias isn't poisoned and marries their "Niece" to settle the succession dispute in Castile. I also think Isabella being in England during the Wars of The Roses to be interesting, as she'd give Margaret d'Anjou a run for her money....
Edward IV of England (b.1442, d.1490) (1) m. Isabella of Castile, Queen of England in 1466 (b.1451, d.1506) had issue
1) Elizabeth of York, Holy Roman Empress (b.1466, d.1518) m. Maximillian I, Holy Roman Emperor (b.1459, d.1519) in 1483, had issue
2) Stillborn son (b.1468)
3) Edward, Prince of Wales, later Edward V of England (b.1471, d.1535) m. Anne of Brittany, Queen of England (b.1477, d.1514) had issue, including Edmund I of England (b.1495) second marriage to Susanna of Bavaria (b.1502, d.1543) had issue
4) Richard, Duke of York (b.1473, d.1492) m. Margaret of York, Suo Jure Duchess of Gloucester in 1490 (b.1475, d.1530) had issue, including Edmund, Duke of York (b.1490) and Richard, Duke of Gloucester (b.1492) (2)
5) Cecily of York, Queen of Scots (b.1475, d.1537) m. James IV of Scotland (b.1473, d.1533) had issue
6) Mary of York, Queen of Castile (b.1479, d.1539) m. Enrique V of Castile (3) (b.1482, d.1545) had issue
7) Eleanor of York, Queen of Denmark, and Norway (b.1479, d.1550) m. Christian II of Denmark and Norway(b.1481, d.1559) had issue
8) John, Duke of Somerset (b.1484, d.1557) m. Alice de la Pole, Suo Jure Countess of Lincoln (4) (b.1485, d.1549), had issue
(1) I imagine that Isabella would be much more concerned about her husband's gluttony than Elizabeth Woodville, and would try to curb it, thus he lives longer (Though if he still died in 1483 per IOTL, a clash between Isabella and her brother-in-law Richard would be interesting)
(2) Daughter of Richard Duke of Gloucester and Anne Neville, since Richard dies of illness in 1488 she inherits his lands, becoming the greatest heiress of all England and naturally marries her young cousin, until he dies of Tuberculosis.
(3) Eldest surviving son of Juana la Beltraneja I of Castile and her "half-uncle" husband Alfonso XII.
(4) Daughter and heiress of John de la Pole, 1st Earl of Lincoln, who dies in a hunting accident in 1488